bluuebunny/crossref_metadata_2025 huggingface dataset:
The Importance of the Fourth wheel in a Four-wheeled Omni Directional Mobile Robot-An Experimental Analysis
Authors: Mohanraj A P , Parameshwaran P , Sivasubramaniyan B P , Srinivasan P , Nijanthan V
Published: October 2023

A four-wheeled Omni Directional Robot may travel in any direction without turning its wheels. In this research work, four Omni-directional wheels have been placed at 90°. This four-wheeled, omnidirectional mobile robot appears to be a square design from the top view, with its wheel axes at 90 degrees. Power is given to the front wheel using a DC motor and that wheel alone will rotate. All other three wheels (Right, Left and Back) are kept in neutral positions. These wheels can move based on the front wheel’s rotation. No power given to these wheels. Three different practical analyses have been done. In this first experimental analysis, the back wheel is kept as an Omni direction wheel. In this Second experimental analysis, the back wheel is kept as a Roller wheel. In this Third experimental analysis, the back wheels are removed and the other three wheels are kept and analysis is done. The importance of the back wheel in the four-wheeled Omni Directional Robot is demonstrated in this research work.
IoT-based Smart Gardening System
Authors: Choudhari Gauri R , Dagale Pratik A , Dashetwar Isha S , Desai Rutuja R , Marathe Abha A
Published: October 2023

Through this project, an IoT based smart garden system has been built which allows the user to monitor various parameters related to the plant including moisture-level, temperature, humidity and light condition. The soil moisture can be regulated with the help of the watering system which can be controlled by the user or operated on automatic mode. The automatic watering system that is provided besides manual mode regulated soil moisture without the need of human intervention. Fertilizer dispenser has been incorporated in the system. This ensures that the plant will get all the required nutrients. The system is Wi-Fi-based and it is supported by a smartphone application and a web dashboard. This makes the monitoring and controlling functions easy and convenient. Since the data is transferred to online database via internet, the data can be retrieved from any location. Thus, there is no limitation of range and it is especially useful if the user is travelling.
Design and analysis of robot and fixture pedestal for OTC FD-V8 MAG welding robot
Authors: Natesan Nandan , Jegadeeshwaran R , Sakthivel G , Arunkumar V
Published: October 2023

The use of automation in the welding process is favoured due to its capacity to enhance the welding quality and expedite the completion of the task. Welding is a commonly automated process in assembly lines, with many companies relying on robotic welding due to its efficient nature. The key advantages of an automated welding process include higher-quality welds, increased productivity, reduced waste production, and lower labour costs. Gas Metal Arc Welding (GMAW) is of two types: namely, Metal Inert Gas (MIG) welding or Metal Active Gas (MAG) welding. GMAW is a welding process that involves a welding gun through which a wire electrode and a shielding gas are fed continuously. This process is commonly performed using a direct current power source with constant voltage, but other types of power sources can also be used. GMAW offers four primary methods of metal transfer, namely globular, short-circuiting, spray, and pulsed-spray, each of which has its unique properties and benefits as well as limitations. In this study, the OTC FD-V8 model robot is used for welding. The pedestal for the robot is designed using SOLIDWORKS and the static analysis of the robot pedestal is done. The fixture is used to hold the work piece for welding. The quality of the weld bead is determined by parameters like voltage, welding current, wire diameter, and composition of the shielding gas.
Analyzing the effect of Process Parameters on Amaranth Popping and Puffing in the Lahi Machine using the Taguchi Method
Authors: Khot Aniket B. , Patil Sagar Dnyandev , Patil Vikas S.
Published: October 2023

Purpose - Amaranth grains are popped by various methods of heating like Oven puffing, Gun puffing, Extrusion puffing, Oil puffing, Pan Popping, etc. Popping of amaranth grains in an oven, gun, extrusion, oil, pan, etc. are having the limitation due to its size, puffing quality, low volume expansion ratio, etc. In this research work the Special Purpose Machine (SPM) with a heating plate was used to pop/puff the amaranth grains. This machine was designed to overcome all the above limitations mentioned earlier. The quality of amaranth grains are depending on temperature, angle, hole size of the nozzle, the material of the heating plate, etc. The impact of these process parameters is analyzed on the Popping Yield (PY), Ratio of Volume Expansion (VER), and Sensory Score (SS) of amaranth grains. The Popping Yield (PY), Ratio of Volume Expansion (VER), and Sensory Score (SS) are major quality parameters of amaranth grains. Therefore these parameters are finalized to carry out further research. The intent of this study is to analyze the more significant process parameters which are impacting PY, VER, and SC.

Methodology – The Taguchi approach was adopted for analyzing the impact of process parameters on the quality of Amaranth grains. The Minitab 17 software was used to detect the significant factors.

Findings – To identify the significant process parameters the design of the experiment (DOE) has been done. L16 Orthogonal Array (OA) has been obtained to carry out the experimental investigation. It was observed that temperature and material of the heating plate are the more significant parameters on PY, VER, and SS. Through investigation of the S/N ratio and ANOVA, it was detected that the temperature and Material are significant parameters and contributed 29.93%, 44.34%, 49.06%, and 44.58%, 28.73%, 29.33% respectively on Popping Yield, Ratio of Volume Expansion and Sensory Score.
Experimentation and 2D Fluid Flow Simulation over an External Gear Pump
Authors: Adake Dhananjay G , Dhote Nihal D , Khond Mohan P
Published: October 2023

In this work, the investigation’s goal is to conduct experiments and simulations on the existing gear pump test rig setup. The various parameters are set and observed in the first section of the investigation. Calculations are done using these numbers to obtain the other testing results. Another section simulates 2-D fluid flow over an external gear pump and contrasts the findings of the experiment with the flow rate and efficiency at various discharge pressures. This study provides a clear understanding of the external gear pump’s numerical analysis as well as its actual analysis. For each discharge pressure at the end, a prediction of pressure at various locations within the pump’s fluid domain was made.
In Cabin Driver Monitoring and Alerting System For Passenger cars using Machine Learning.
Authors: Suryavanshi Shrirang , Ladhwe Raju , Joshi Omkar
Published: October 2023

The primary causes of road accidents are driver errors. Such as excessive speeding, driver distraction, and driver sleepiness. Diver sleepiness and distraction can be controlled by implementing advanced technology such as an in-cabin driver monitoring system. This is a technological solution that uses a machine learning algorithm to improve road safety. This paper describes a new real-time driver monitoring and alerting system that solely monitors driver Sleepiness, diver distraction, and seatbelt wearing status in order to prevent road accidents. It employs the YOLOv5 deep learning algorithm to detect various types of distraction and For seatbelt wearing status and computer vision’s cvzone framework is used to detect sleepiness using 3D facial landmarking. In this system, The camera is mounted in the centre of the vehicle’s dashboard for data collection and real-time implementation. The Raspberry Pi 3b module is used for the Realtime implementation. According to the findings of this study, the system is capable of real-time implementation, and the machine learning model used in the study achieves an accuracy of more than 90%.
A Deep Learning model for driver drowsiness detection in extremely low-light conditions
Authors: Anoop P P , Deivanathan R
Published: October 2023

Accidents occurring at night account for a significant percentage when compared to those that happen during the daytime. One of the leading causes of such accidents is driver drowsiness, which could result from inadequate sleep or exhaustion. Continuous monitoring of the facial expressions of the driver can detect signs of drowsiness, and an alarm system can alert the driver and prevent potential accidents. Various research studies have been conducted in this area. However, the low lighting conditions at night make it challenging to obtain detailed images, making it difficult to apply the proposed models effectively. This paper presents an effective model for detecting driver drowsiness using deep learning techniques. The study utilizes AlexNet as a classifier and attains an impressive accuracy of 98.3% after hyperparameter tuning.
Recent development of LIF diagnostics in ASIPP
Authors: Yip Chi-Shung , Jiang Di , Jin Chenyao , Zhang Wei
Published: October 2023

In this article, recent research progress of laser induced fluorescence (LIF) diagnostics in ASIPP is reviewed. The fundamental goal of ASIPP's effort on the LIF diagnostics is to develop a working velocity distribution function (VDF) diagnostic to monitor helium ash removal in burning plasmas. Real-time monitoring of helium ash VDF requires consideration in radiation safety, measurement response time, and compatibility of tokamak operation, as well as ion/neutral VDFs with a temperature at possibly >20 eV. These considerations, almost unique to large-scale instruments or specifically to tokamak plasmas, require renewed research and development (R&D) efforts in optical design, automation, and expansion of laser functionality for the LIF diagnostics that were often not considered in conventional applications of the LIF diagnostics. To this end, ASIPP invested a series of research effort into the development of LIF techniques. Signal evaluation has been performed on a diagnostics-test device (LTS), and the obtained signal strength has been extrapolated to tokamak edge and divertor relevant environments with promising results. The extrapolations compared the available solid angle and plasma density between the test device and the design scenario where the LIF diagnostics will potentially be implemented in a tokamak edge and divertor plasma. The estimation neglects the higher density of energetic electrons in the edge and divertor regions, making it a conservative assessment. Automated post-DAQ processing of LIF signals using both “conventional” methods and an AI-augmented method were also explored. Both approaches yielded usable results, but the AI-trained method showed a faster response, which is advantageous for real-time plasma diagnostics. Basic mechanisms of LIF diagnostics were also explored. Specifically, the limitations of lock-in modulation was demonstrated to determine the limitation of time-resolved measurements using such methods. De-modulation and degradation of the LIF signal occurred as the modulation frequency exceeded 1/10th of the fluorescence frequency. This finding sets a practical limit of the modulation frequency up to which we can benefit from lock-in amplification. These published works along with other unpublished progress will be thoroughly discussed in this article to illustrate ASIPP's effort towards the implementation of LIF diagnostics in future tokamak devices and to promote the application of LIF diagnostics in other fields of research.
Carbon dioxide release from retrogressive thaw slumps in Siberia
Authors: Beer C , Runge A , Grosse G , Hugelius G , Knoblauch C
Published: October 2023

Thawing of ice-rich permafrost soils in sloped terrain can lead to activation of retrogressive thaw slumps (RTSs) which make organic matter available for decomposition that has been frozen for centuries to millennia. Recent studies show that the area affected by RTSs increased in the last two decades across the pan-Arctic. Combining a model of soil carbon dynamics with remotely sensed spatial details of thaw slump area and a soil carbon database, we show that RTSs in Siberia turned a previous quasi-neutral ecosystem into a strong source of carbon dioxide of 367 ± 213 gC m-1 a-1. On a global scale, recent CO2 emissions from Siberian thaw slumps of 0.42 ± 0.22 Tg carbon per year are negligible so far. However, depending on the future evolution of permafrost thaw and hence thaw slump-affected area, such hillslope processes can transition permafrost landscapes to become a major source of additional CO2 release into the atmosphere.
Serengeti–Masai Mara ecosystem dynamics inferred from rainfall extremes
Authors: Mtewele Zacharia Florence , Jia Gensuo , Xu Xiyan
Published: October 2023

The Serengeti–Masai Mara Ecosystem (SMME) is an iconic ecological and biodiversity resource in East Africa with a spectacular great animal migration feature. Environmental shocks like droughts, floods, and land degradation threaten the SMME’s ecological functioning. However, the spatiotemporal ecosystem dynamics during climate extremes are inadequately examined. Here we quantified water availability and vegetation changes during extreme wet (EWE) and dry (EDE) events over the SMME for wet and dry seasons in 1982–2020. We derived extreme events from seasonal mean precipitation anomaly exceeding standard deviation and applied composite and correlation techniques to assess their dynamics with animal populations and migration prospects. Wet season EWE increases vegetative and moist conditions over southern SMME, suggesting elongating migrants’ occupancy compared to normal periods and delayed northward migration. Wet season EDE significantly suppresses these features, heightening ecosystem competition and survival threats, proposing an earlier northward migration. Dry season EWE increases vegetation and water availability over northern SMME, prompting the late southward migration. Dry season EDE significantly reduces vegetation and water availability over northern SMME, suggesting an early southward migration towards regions with more vegetation and increased water availability. The SMME also experiences multiple EDE occurring in consecutive seasons, prolonging dry conditions that aggregate wildlife survival threats. Notably, two EDE prevailed consecutively from the 1993 dry season to the 1994 wet season, coupled with a population decline of wildebeest (1.2–0.9 million), buffalo (40–20 thousand), and lion (1.3–0.9 thousand). We also note a reversal from more EDE to EWE during the study period. Prevalent EWE can lessen wet and vegetative conditions distribution gradient, which is imperative for the functioning of the SMME migratory ecosystem. Our study unveiled hotspot areas of extremes-driven ecosystem changes for the sustainable SMME migratory functioning essential for framing meaningful conservation management policies under climate change.
Integrability and BRST invariance from BF topological theory
Authors: Restuccia A , Sotomayor A
Published: October 2023

We consider the Becchi, Rouet, Stora and Tyutin (BRST) invariant effective action of the non-abelian BF topological theory in two dimensions with gauge groupSl(2,R). By considering different gauge fixing conditions, the zero-curvature field equation gives rise to several well known integrable equations. We prove that each integrable equation together with the associated ghost field evolution equation, obtained from the BF theory, is a BRST invariant system with an infinite sequence of BRST invariant conserved quantities. We construct explicitly the systems and the BRST transformation laws for the Korteweg-de Vries (KdV) sequence (including the KdV, mKdV and CKdV equations) and Harry Dym integrable equation.
Concerning the direction of the Aharonov–Bohm deflection
Authors: Boyer Timothy H
Published: October 2023

The interaction of a solenoid with a passing charged particle can be treated within classical or quantum physics. If charged particles pass around both sides of a solenoid, there is an experimentally-observed Aharonov–Bohm deflection of the double-slit particle interference pattern between charges passing on opposite sides. Such a deflection can be obtained by a classical force calculation. Although the magnitude of the angular deflection agrees between the classical force calculation and the quantum topological theory, the direction of the predicted deflection is opposite. Here we point out the simple basis for the direction of the deflection based upon classical electrodynamics and based upon quantum theory. Also, we mention some deflection analogs, both the electrostatic deflection of the particle interference pattern and the optical analog of the classical calculation. The deflection direction involves an experimental question which is addressed rarely if ever. In the deflection direction, there is a direct experimental confrontation connected with the long-standing controversy involving the interpretation of the Aharonov–Bohm phase shift.
Doing it all: Effects of Family Responsibilities and Marital Relationship Quality on Mothers’ Ambulatory Blood Pressure
Authors: Graff Tyler C , Birmingham Wendy C , Wadsworth Lori L , Hung Man
Published: October 2023

Background

The shared provider responsibility between married couples does not translate to equally shared division of childcare (CC) and household labor. While some marriages contain highly positive aspects, marriages may also simultaneously contain both positive and negative aspects. The negativity in these relationships can negate the positivity and could potentially lead to the detriment of mothers’ health.

Purpose

We examined mothers’ ambulatory blood pressure (ABP) associated with their marital relationship quality and perceived equity with her spouse on CC and household tasks.

Methods

We investigate these associations using a mixed multilevel model analysis on a sample of 224 mothers in heterosexual marriages, all of whom had children under the age of 18 years currently living in the home.

Results

Mothers’ perception of equity in the division of CC responsibilities contributed to lower ABP. Additionally, mothers in supportive marital relationships (low negativity and high positivity) had lower ABP than those in ambivalent relationships (both high negativity and positivity). There was a crossover interaction such that the effect of relationship quality on ABP was moderated by the perception of equity in the division of CC. For mothers who report doing all the CC, they had lower ABP if they had a supportive marital relationship compared with mothers in ambivalent relationships. Whereas mothers who report more equity in CC and have a supportive relationship have higher ABP compared with mothers in ambivalent relationships.

Conclusions

This study has implications related to dynamics within marital relationships. These results demonstrate important relational influences on mothers’ ABP.
Belief as Status: Premodern Islamic Law, Duties, and the Martyr Conundrum
Authors: Zulfiqar Adnan A
Published: October 2023

The normative universe of the premodern Islamic legal tradition revolves around duties. These duties are determined by an individual’s status both as an autonomous entity and as part of the collective. The duties one owes and those that one is owed, are primarily constructed around belief. Belief, and its absence, function as the primary vehicles for affirming or denying an individual’s place within the moral community. In the jurists discourse on warfare, during the fifth ah/eleventh ce and sixth ah/twelfth ce centuries, we find an illustrative example of how belief dictates the duties that must be performed. Who is obligated to fight, who must be fought, and what obligations are owed in death all depend, though not exclusively, on the belief status of the relevant actors. In the process jurists constructed status hierarchies based on belief and, as in the case of martyrs, negotiated a delicate balance between preserving the sacredness of belief status and accounting for the pragmatic requirements of the battlefield.
Religious Endowments in Ancient India and the Institutionalization of Brahmin Caste Status
Authors: Lubin Timothy
Published: October 2023

Giving to worthy recipients has been meritorious public piety in India at least since the Mauryan empire. Most consequential were grants in perpetuity of land or capital as a ‘religious foundation’ for monks or Brahmins, conferred by means of a charter (śāsana). Grants to Brahmins typically created or supported an agrahāra, a residential enclave with attached farmland and villages, on terms analogous to those of grants to Buddhist or Jaina mendicants or monasteries. In these records (attested since the beginning of the Common Era), rulers cede their claims to certain normal obligations of subjects, such as tax revenue, compulsory labor, and billeting or provisions for officers of the state, and they often give the beneficiaries authority over internal legal administration. This article examines the implications of the fiscal and juridical autonomy conferred in such grants in providing state recognition and institutional support of Brahmins’ sacred status as a religious profession and a privileged caste.
Decoding functional cell–cell communication events by multi-view graph learning on spatial transcriptomics
Authors: Li Haochen , Ma Tianxing , Hao Minsheng , Guo Wenbo , Gu Jin , Zhang Xuegong , Wei Lei
Published: October 2023

Cell–cell communication events (CEs) are mediated by multiple ligand–receptor (LR) pairs. Usually only a particular subset of CEs directly works for a specific downstream response in a particular microenvironment. We name them as functional communication events (FCEs) of the target responses. Decoding FCE-target gene relations is: important for understanding the mechanisms of many biological processes, but has been intractable due to the mixing of multiple factors and the lack of direct observations. We developed a method HoloNet for decoding FCEs using spatial transcriptomic data by integrating LR pairs, cell-type spatial distribution and downstream gene expression into a deep learning model. We modeled CEs as a multi-view network, developed an attention-based graph learning method to train the model for generating target gene expression with the CE networks, and decoded the FCEs for specific downstream genes by interpreting trained models. We applied HoloNet on three Visium datasets of breast cancer and liver cancer. The results detangled the multiple factors of FCEs by revealing how LR signals and cell types affect specific biological processes, and specified FCE-induced effects in each single cell. We conducted simulation experiments and showed that HoloNet is more reliable on LR prioritization in comparison with existing methods. HoloNet is a powerful tool to illustrate cell–cell communication landscapes and reveal vital FCEs that shape cellular phenotypes. HoloNet is available as a Python package at https://github.com/lhc17/HoloNet.
Longitudinal remote monitoring of hidradenitis suppurativa: a pilot study
Authors: Fonjungo Fonette E , Barnes Leandra A , Cai Zhuo Ran , Naik Haley B , Eid Edward S , Aleshin Maria A , Nava Vanessa , Johnson Tiffani , Chren Mary-Margaret , Linos Eleni
Published: October 2023

We sought to investigate the feasibility of longitudinal monitoring of disease activity from home in people with hidradenitis suppurativa (HS). Over 6 months, our novel digital tool collected 421 photos of HS-affected skin from 27 participants and captured trends in pain and quality of life scores. We found that participants with mild disease were more likely to share their progress than those with more severe disease, which is favourable as it may suggest a role for remote monitoring in tracking disease progression. This pilot provides proof of concept that will support future studies.
Daily Oral HIV Pre-exposure Prophylaxis Among Young Men Who Have Sex With Men in the United States: Cost-saving at Generic Drug Price
Authors: Amick Alyssa K , Eskibozkurt G Ege , Hosek Sybil G , Flanagan Clare F , Landovitz Raphael J , Jin Elena Y , Wilson Craig M , Freedberg Kenneth A , Weinstein Milton C , Kazemian Pooyan , Paltiel A David , Ciaranello Andrea L , Neilan Anne M
Published: October 2023

Background

Adherence and retention concerns raise questions about the effectiveness and cost-effectiveness of oral HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM).

Methods

Using an adolescent-focused simulation model, we compared annual HIV screening alone with tenofovir disoproxil fumarate/emtricitabine–based oral PrEP with every 3-month HIV screening in YMSM (aged 15–24) at increased risk of HIV. Data derived from published sources included: age-stratified HIV incidence/100 person-years (PY) on- or off-PrEP (0.6–10.1 or 0.4–6.4), PrEP retention at 6 years (28%), transmissions by HIV RNA level (0.0–78.4/100PY) and annual costs of antiretroviral therapy ($32 000–69 000), HIV care ($3100–34 600), and PrEP program/generic drug ($900/360). Outcomes included transmissions (percent of cohort infected), quality-adjusted life-years (QALYs), costs ($), and incremental cost-effectiveness ratios ($/QALY). We explored the sensitivity of findings to variation in HIV incidence and drug prices.

Results

Compared with annual screening alone, PrEP would increase QALYs (9.58 to 9.67), reduce new infections (37% to 30%), and decrease costs (by $5000) over 10 years. PrEP would remain cost-saving for HIV incidence off-PrEP ≥5.1/100PY or annual PrEP price ≤$1200. Over a lifetime horizon, PrEP would be cost-saving for HIV incidence off-PrEP ≥1.0/100PY, across all retention assumptions examined. PrEP would not be cost-effective at HIV incidence ≤0.1/100PY, regardless of drug price, due to programmatic costs.

Conclusions

In US YMSM at increased risk of HIV, generic oral PrEP and every-3-month screening would be cost-saving compared with annual screening alone, even with high discontinuation and low adherence, over a range of HIV incidences.
Febrile Phase Soluble Urokinase Plasminogen Activator Receptor and Olfactomedin 4 as Prognostic Biomarkers for Severe Dengue in Adults
Authors: Teo Andrew , Le Chau Thuy Tien , Tan Trevor , Chia Po Ying , Yeo Tsin Wen
Published: October 2023

Background

Dengue cases continue to rise and can overwhelm healthcare systems during outbreaks. In dengue, neutrophil mediators, soluble urokinase plasminogen activator receptor (suPAR) and olfactomedin 4, and mast cell mediators, chymase and tryptase, have not been measured longitudinally across the dengue phases. The utility of these proteins as prognostic biomarkers for severe dengue has also not been assessed in an older adult population.

Methods

We prospectively enrolled 99 adults with dengue—40 dengue fever, 46 dengue with warning signs and 13 severe dengue, along with 30 controls. Plasma levels of suPAR, olfactomedin 4, chymase and tryptase were measured at the febrile, critical and recovery phases in dengue patients.

Results

The suPAR levels were significantly elevated in severe dengue compared to the other dengue severities and controls in the febrile (P < .001), critical (P < .001), and recovery (P = .005) phases. In the febrile phase, suPAR was a prognostic biomarker of severe dengue, with an AUROC of 0.82. Using a cutoff derived from Youden's index (5.4 ng/mL) and an estimated prevalence of severe dengue (16.5%) in our healthcare institution, the sensitivity was 71.4% with a specificity of 87.9% in the febrile phase, and the positive and negative predictive values were 54.7% and 95.8%, respectively. Olfactomedin 4 was elevated in dengue patients but not in proportion to disease severity in the febrile phase (P = .04) There were no significant differences in chymase and tryptase levels between dengue patients and controls.

Conclusions

In adult dengue, suPAR may be a reliable prognostic biomarker for severe dengue in the febrile phase.
Forest canopy mortality during the 2018-2020 summer drought years in Central Europe: The application of a deep learning approach on aerial images across Luxembourg
Authors: Schwarz Selina , Werner Christian , Fassnacht Fabian Ewald , Ruehr Nadine K
Published: October 2023

Efficient monitoring of tree canopy mortality requires data that cover large areas and capture changes over time while being precise enough to detect changes at the canopy level. In the development of automated approaches, aerial images represent an under-exploited scale between high-resolution drone images and satellite data. Our aim herein was to use a deep learning model to automatically detect canopy mortality from high-resolution aerial images after severe drought events in the summers 2018–2020 in Luxembourg. We analysed canopy mortality for the years 2017–2020 using the EfficientUNet++, a state-of-the-art convolutional neural network. Training data were acquired for the years 2017 and 2019 only, in order to test the robustness of the model for years with no reference data. We found a severe increase in canopy mortality from 0.64 km2 in 2017 to 7.49 km2 in 2020, with conifers being affected at a much higher rate than broadleaf trees. The model was able to classify canopy mortality with an F1-score of 66%–71% and we found that for years without training data, we were able to transfer the model trained on other years to predict canopy mortality, if illumination conditions did not deviate severely. We conclude that aerial images hold much potential for automated regular monitoring of canopy mortality over large areas at canopy level when analysed with deep learning approaches. We consider the suggested approach a cost-efficient and -effective alternative to drone and field-based sampling.
Real-world experience of therapeutic drug monitoring and PK/PD achievement of ceftaroline administered by different infusion regimens in patients with confirmed infections caused by Gram-positive bacteria
Authors: Fresán Daniel , Luque Sonia , Benítez-Cano Adela , Sorlí Luisa , Montero María Milagro , De-Antonio Marta , Vega Victoria , Roberts Jason A , Horcajada Juan P , Grau Santiago
Published: October 2023

Background

Ceftaroline is a novel cephalosporin active against MDR Gram-positive (GP) bacteria. For β-lactam antibiotics, such as ceftaroline, prolonged infusions and therapeutic drug monitoring (TDM) are used for dosage optimization based on their pharmacokinetics/pharmacodynamics (PK/PD).

Objectives

To describe our experience with TDM and PK/PD target attainment of ceftaroline administered by intermittent and prolonged infusion in a cohort of patients with MDR-GP bacterial infections.

Methods

Patients treated with ceftaroline administered by continuous (24 h), extended (3 h/6 h) and intermittent infusion (1 h) and undergoing TDM of plasma concentrations were included. A 100%fT>4×MIC was the pre-specified PK/PD target and 100%fT>10×MIC was considered overexposure. Dose recommendations were made based on TDM results and each patient’s clinical condition.

Results

Twelve patients [83.3% male, median age of 73 (38–83) years] were included. Nine patients (75%) achieved 100%fT>4×MIC, all under prolonged infusions. In one patient, the 100%fT was >10×MIC but no toxicity was observed. Based on TDM results, initial doses were recommended to be maintained in eight patients, decreased in three and increased in one.

Conclusions

The administration of ceftaroline by prolonged infusion together with TDM may be a useful strategy for achieving the desired PK/PD target in these patients. However, more studies evaluating the relationship between PK/PD attainment and clinical outcomes are needed.
Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis
Authors: Bock Magnus , Van Hasselt Johan G C , Schwartz Franziska , Wang Hengzhuang , Høiby Niels , Fuursted Kurt , Ihlemann Nikolaj , Gill Sabine , Christiansen Ulrik , Bruun Niels Eske , Elming Hanne , Povlsen Jonas A , Køber Lars , Høfsten Dan E , Fosbøl Emil L , Pries-Heje Mia M , Christensen Jens Jørgen , Rosenvinge Flemming S , Torp-Pedersen Christian , Helweg-Larsen Jannik , Tønder Niels , Iversen Kasper , Bundgaard Henning , Moser Claus
Published: October 2023

Background

Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci.

Objectives

Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated.

Patients and methods

Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination.

Results

We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%–251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively.

Conclusions

A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.
Ancestry testing of “Old Tom,” a killer whale central to mutualistic interactions with human whalers
Authors: Reeves Isabella M , Totterdell John A , Betty Emma L , Donnelly David M , George Angela , Holmes Steven , Moller Luciana , Stockin Karen A , Wellard Rebecca , White Charlie , Foote Andrew D
Published: October 2023

Cooperative hunting between humans and killer whales (Orcinus orca) targeting baleen whales was reported in Eden, New South Wales, Australia, for almost a century. By 1928, whaling operations had ceased, and local killer whale sightings became scarce. A killer whale from the group, known as “Old Tom,” washed up dead in 1930 and his skeleton was preserved. How these killer whales from Eden relate to other populations globally and whether their genetic descendants persist today remains unknown. We extracted and sequenced DNA from Old Tom using ancient DNA techniques. Genomic sequences were then compared with a global dataset of mitochondrial and nuclear genomes. Old Tom shared a most recent common ancestor with killer whales from Australasia, the North Atlantic, and the North Pacific, having the highest genetic similarity with contemporary New Zealand killer whales. However, much of the variation found in Old Tom’s genome was not shared with these widespread populations, suggesting ancestral rather than ongoing gene flow. Our genetic comparisons also failed to find any clear descendants of Tom, raising the possibility of local extinction of this group. We integrated Traditional Custodian knowledge to recapture the events in Eden and recognize that Indigenous Australians initiated the relationship with the killer whales before European colonization and the advent of commercial whaling locally. This study rectifies discrepancies in local records and provides new insight into the origins of the killer whales in Eden and the history of Australasian killer whales.
Clinical benefit, development, innovation, trials, epidemiology, and price for cancer drugs and indications with multiple special FDA designations
Authors: Michaeli Daniel Tobias , Michaeli Thomas , Albers Sebastian , Michaeli Julia Caroline
Published: October 2023

Background

This study analyzes the development, US Food and Drug Administration (FDA) approval, benefits, innovation, trials, epidemiology, and price of cancer drugs with multiple special designations: orphan, fast track, accelerated approval, priority review, and breakthrough therapy.

Methods

In total, 355 FDA-approved cancer drug indications with 841 special designations were identified (2012-2022). Trial, epidemiology, and price data were collected from FDA labels, the Global Burden of Disease study, and Medicare and Medicaid. The association between efficacy outcomes and indications’ number of special designations were compared in meta-analyses.

Results

Median development times were 7.3, 7.8, and 5.4 months (P = .027) for drugs with 0 to 1, 2 to 3, and 4 to 5 special designations, respectively. Multiple special designations were associated with higher biotechnological and clinical innovation. Median patient enrollment in trials were 615, 471, 398, 168, 104, and 120 (P < .001) for indications with 0 to 5 special designations. Drugs for rare diseases supported by open-label phase 1/2 trials of single-arm design were granted more special designations. Hazard ratios for overall survival (0.80 vs 0.73 vs 0.73 vs 0.69 vs 0.56 vs 0.52; P = .003) and progression-free survival (0.70 vs 0.61 vs 0.59 vs 0.44 vs 0.37 vs 0.67; P < .001) substantially declined while tumor response increased with more special designations. Mean monthly prices increased for drugs with 0 to 4 but not 5 special designations ($21 596 vs $14 753 vs $32 410 vs $41 240 vs $38 703 vs $19 184).

Conclusions

Multiple special designations are associated with faster clinical development and greater benefits for patients with unmet needs but also with nonrobust trial evidence and a tendency toward higher drug prices.
Phylogenomics Reveals High Levels of Incomplete Lineage Sorting at the Ancestral Nodes of the Macaque Radiation
Authors: Tan Xinxin , Qi Jiwei , Liu Zhijin , Fan Pengfei , Liu Gaoming , Zhang Liye , Shen Ying , Li Jing , Roos Christian , Zhou Xuming , Li Ming
Published: October 2023

The genus Macaca includes 23 species assigned into 4 to 7 groups. It exhibits the largest geographic range and represents the most successful example of adaptive radiation of nonhuman primates. However, intrageneric phylogenetic relationships among species remain controversial and have not been resolved so far. In this study, we conducted a phylogenomic analysis on 16 newly generated and 8 published macaque genomes. We found strong evidence supporting the division of this genus into 7 species groups. Incomplete lineage sorting (ILS) was the primary factor contributing to the discordance observed among gene trees; however, we also found evidence of hybridization events, specifically between the ancestral arctoides/sinica and silenus/nigra lineages that resulted in the hybrid formation of the fascicularis/mulatta group. Combined with fossil data, our phylogenomic data were used to establish a scenario for macaque radiation. These findings provide insights into ILS and potential ancient introgression events that were involved in the radiation of macaques, which will lead to a better understanding of the rapid speciation occurring in nonhuman primates.
The landscape of human SVA retrotransposons
Authors: Chu Chong , Lin Eric W , Tran Antuan , Jin Hu , Ho Natalie I , Veit Alexander , Cortes-Ciriano Isidro , Burns Kathleen H , Ting David T , Park Peter J
Published: October 2023

SINE-VNTR-Alu (SVA) retrotransposons are evolutionarily young and still-active transposable elements (TEs) in the human genome. Several pathogenic SVA insertions have been identified that directly mutate host genes to cause neurodegenerative and other types of diseases. However, due to their sequence heterogeneity and complex structures as well as limitations in sequencing techniques and analysis, SVA insertions have been less well studied compared to other mobile element insertions. Here, we identified polymorphic SVA insertions from 3646 whole-genome sequencing (WGS) samples of >150 diverse populations and constructed a polymorphic SVA insertion reference catalog. Using 20 long-read samples, we also assembled reference and polymorphic SVA sequences and characterized the internal hexamer/variable-number-tandem-repeat (VNTR) expansions as well as differing SVA activity for SVA subfamilies and human populations. In addition, we developed a module to annotate both reference and polymorphic SVA copies. By characterizing the landscape of both reference and polymorphic SVA retrotransposons, our study enables more accurate genotyping of these elements and facilitate the discovery of pathogenic SVA insertions.
Phosphate starvation regulates cellulose synthesis to modify root growth
Authors: Khan Ghazanfar Abbas , Dutta Arka , van de Meene Allison , Frandsen Kristian E H , Ogden Michael , Whelan James , Persson Staffan
Published: October 2023

In the model plant Arabidopsis (Arabidopsis thaliana), the absence of the essential macro-nutrient phosphate reduces primary root growth through decreased cell division and elongation, requiring alterations to the polysaccharide-rich cell wall surrounding the cells. Despite its importance, the regulation of cell wall synthesis in response to low phosphate levels is not well understood. In this study, we show that plants increase cellulose synthesis in roots under limiting phosphate conditions, which leads to changes in the thickness and structure of the cell wall. These changes contribute to the reduced growth of primary roots in low-phosphate conditions. Furthermore, we found that the cellulose synthase complex (CSC) activity at the plasma membrane increases during phosphate deficiency. Moreover, we show that this increase in the activity of the CSC is likely due to alterations in the phosphorylation status of cellulose synthases in low-phosphate conditions. Specifically, phosphorylation of CELLULOSE SYNTHASE 1 (CESA1) at the S688 site decreases in low-phosphate conditions. Phosphomimic versions of CESA1 with an S688E mutation showed significantly reduced cellulose induction and primary root length changes in low-phosphate conditions. Protein structure modeling suggests that the phosphorylation status of S688 in CESA1 could play a role in stabilizing and activating the CSC. This mechanistic understanding of root growth regulation under limiting phosphate conditions provides potential strategies for changing root responses to soil phosphate content.
Analgesic prescribing in patients with inflammatory arthritis in England: observational studies in the Clinical Practice Research Datalink
Authors: Scott Ian C , Whittle Rebecca , Bailey James , Twohig Helen , Hider Samantha L , Mallen Christian D , Muller Sara , Jordan Kelvin P
Published: October 2023

Objectives

Despite little evidence that analgesics are effective in inflammatory arthritis (IA), studies report substantial opioid prescribing. The extent this applies to other analgesics is uncertain. We undertook a comprehensive evaluation of analgesic prescribing in patients with IA in the Clinical Practice Research Datalink Aurum to evaluate this.

Methods

From 2004 to 2020, cross-sectional analyses evaluated analgesic prescription annual prevalence in RA, PsA and axial spondyloarthritis (axSpA), stratified by age, sex, ethnicity, deprivation and geography. Joinpoint regression evaluated temporal prescribing trends. Cohort studies determined prognostic factors at diagnosis for chronic analgesic prescriptions using Cox proportional hazards models.

Results

Analgesic prescribing declined over time but remained common: 2004 and 2020 IA prescription prevalence was 84.2/100 person-years (PY) (95% CI 83.9, 84.5) and 64.5/100 PY (64.2, 64.8), respectively. In 2004, NSAIDs were most prescribed (56.1/100 PY; 55.8, 56.5), falling over time. Opioids were most prescribed in 2020 (39.0/100 PY; 38.7, 39.2). Gabapentinoid prescribing increased: 2004 prevalence 1.1/100 PY (1.0, 1.2); 2020 prevalence 9.9/100 PY (9.7, 10.0). Most opioid prescriptions were chronic (2020 prevalence 23.4/100 PY [23.2, 23.6]). Non-NSAID analgesic prescribing was commoner in RA, older people, females and deprived areas/northern England. Conversely, NSAID prescribing was commoner in axSpA/males, varying little by deprivation/geography. Peri-diagnosis was high-risk for starting chronic opioid/NSAID prescriptions. Prognostic factors for chronic opioid/gabapentinoid and NSAID prescriptions differed, with NSAIDs having no consistently significant association with deprivation (unlike opioids/gabapentinoids).

Conclusion

IA analgesic prescribing of all classes is widespread. This is neither evidence-based nor in line with guidelines. Peri-diagnosis is an opportune moment to reduce chronic analgesic prescribing.
Fluid shear stress stimulates ATP release without regulating purinergic gene expression in the renal inner medullary collecting duct
Authors: van Megen Wouter H. , Canki Esra , Wagenaar Vera H. A. , van Waes Charlotte R. M. M. , Peters Dorien J. M. , Van Asbeck‐Van der Wijst Jenny , Hoenderop Joost G. J.
Published: October 2023

In the kidney, the flow rate of the pro‐urine through the renal tubules is highly variable. The tubular epithelial cells sense these variations in pro‐urinary flow rate in order to regulate various physiological processes, including electrolyte reabsorption. One of the mechanosensitive pathways activated by flow is the release of ATP, which can then act as a autocrine or paracrine factor. Increased ATP release is observed in various kidney diseases, among others autosomal dominant polycystic kidney disease (ADPKD). However, the mechanisms underlying flow‐induced ATP release in the collecting duct, especially in the inner medullary collecting duct, remain understudied. Using inner medullary collecting duct 3 (IMCD3) cells in a microfluidic setup, we show here that administration of a high flow rate for 1 min results in an increased ATP release compared to a lower flow rate. Although the ATP release channel pannexin‐1 contributed to flow‐induced ATP release in Pkd1−/− IMCD3 cells, it did not in wildtype IMCD3 cells. In addition, flow application increased the expression of the putative ATP release channel connexin‐30.3 (CX30.3) in wildtype and Pkd1−/− IMCD3 cells. However, CX30.3 knockout IMCD3 cells exhibited a similar flow‐induced ATP release as wildtype IMCD3 cells, suggesting that CX30.3 does not drive flow‐induced ATP release in wildtype IMDC3 cells. Collectively, our results show differential mechanisms underlying flow‐induced ATP release in wildtype and Pkd1−/− IMCD3 cells and further strengthen the link between ADPKD and pannexin‐1‐dependent ATP release.
Incorporating Omics and Precision Health in a Nursing PhD Program: The Perspectives of Student Nurse Scientists
Authors: Flaherty Christine Noelle , Rattan Jesse , Melson Lindsay , O’Neal Pamela V.
Published: October 2023

To engage in innovative and novel precision health and omics research, nurse scientists need to be knowledgeable about the genetic, behavioral, and environmental factors that impact health outcomes. This article illustrates the benefits of a nursing omics PhD curriculum at a state university. The purpose is to provide students’ perspectives and research interests that were inspired by the omics and precision health curriculum. Exposing these early-career PhD nursing student scientists to omics and precision health engaged them to think broadly about the potential to generate original nurse-led research.