bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causes of Death in Patients With Brain Metastases
Authors: Schnurman Zane , Mashiach Elad , Link Katherine E. , Donahue Bernadine , Sulman Erik , Silverman Joshua , Golfinos John G. , Oermann Eric Karl , Kondziolka Douglas 
Published: May 2023

BACKGROUND AND OBJECTIVES:
Advances in targeted therapies and wider application of stereotactic radiosurgery (SRS) have redefined outcomes of patients with brain metastases. Under modern treatment paradigms, there remains limited characterization of which aspects of disease drive demise and in what frequencies. This study aims to characterize the primary causes of terminal decline and evaluate differences in underlying intracranial tumor dynamics in patients with metastatic brain cancer. These fundamental details may help guide management, patient counseling, and research priorities.

METHODS:
Using NYUMets-Brain—the largest, longitudinal, real-world, open data set of patients with brain metastases—patients treated at New York University Langone Health between 2012 and 2021 with SRS were evaluated. A review of electronic health records allowed for the determination of a primary cause of death in patients who died during the study period. Causes were classified in mutually exclusive, but collectively exhaustive, categories. Multilevel models evaluated for differences in dynamics of intracranial tumors, including changes in volume and number.

RESULTS:
Of 439 patients with end-of-life data, 73.1% died secondary to systemic disease, 10.3% died secondary to central nervous system (CNS) disease, and 16.6% died because of other causes. CNS deaths were driven by acute increases in intracranial pressure (11%), development of focal neurological deficits (18%), treatment-resistant seizures (11%), and global decline driven by increased intracranial tumor burden (60%). Rate of influx of new intracranial tumors was almost twice as high in patients who died compared with those who survived (P < .001), but there was no difference in rates of volume change per intracranial tumor (P = .95).

CONCLUSION:
Most patients with brain metastases die secondary to systemic disease progression. For patients who die because of neurological disease, tumor dynamics and cause of death mechanisms indicate that the primary driver of decline for many may be unchecked systemic disease with unrelenting spread of new tumors to the CNS rather than failure of local growth control.
Maturing differentiated human pluripotent stem cells in vitro: methods and challenges
Authors: Ottaviani Daniele , ter Huurne Menno , Elliott David A. , Bellin Milena , Mummery Christine L. 
Published: June 2023

ABSTRACT
Human pluripotent stem cells (hPSCs), derived from individuals or genetically modified with disease-related mutations and variants, have revolutionised studies of human disease. Researchers are beginning to exploit the extraordinary potential of stem cell technology to screen for new drugs to treat intractable diseases, ideally without side-effects. However, a major problem is that the differentiated cell types on which these models are based are immature; they resemble fetal and not adult cells. Here, we discuss the nature and hurdles of hPSC maturation, using cardiomyocytes as an example. We review methods used to induce cardiomyocyte maturation in culture and consider remaining challenges for their integration into research on human disease and drug development pipelines.
deCLUTTER2+ – a pipeline to analyze calcium traces in a stem cell model for ventral midbrain patterned astrocytes
Authors: Grochowska Martyna M. , Ferraro Federico , Mascaro Ana Carreras , Natale Domenico , Winkelaar Amber , Boumeester Valerie , Breedveld Guido J. , Bonifati Vincenzo , Mandemakers Wim 
Published: June 2023

ABSTRACT
Astrocytes are the most populous cell type of the human central nervous system and are essential for physiological brain function. Increasing evidence suggests multiple roles for astrocytes in Parkinson's disease, nudging a shift in the research focus, which historically pivoted around ventral midbrain dopaminergic neurons (vmDANs). Studying human astrocytes and other cell types in vivo remains challenging. However, in vitro-reprogrammed human stem cell-based models provide a promising alternative. Here, we describe a novel protocol for astrocyte differentiation from human stem cell-derived vmDAN-generating progenitors. This protocol simulates the regionalization, gliogenic switch, radial migration and final differentiation that occur in the developing human brain. We characterized the morphological, molecular and functional features of these ventral midbrain patterned astrocytes with a broad palette of techniques and identified novel candidate midbrain-astrocyte specific markers. In addition, we developed a new pipeline for calcium imaging data analysis called deCLUTTER2+ (deconvolution of Ca2+ fluorescent patterns) that can be used to discover spontaneous or cue-dependent patterns of Ca2+ transients. Altogether, our protocol enables the characterization of the functional properties of human ventral midbrain patterned astrocytes under physiological conditions and in disease.
A phosphatidylinositol phosphate kinase inhibits Ras activation and regulates chemorepulsion in Dictyostelium discoideum
Authors: Kirolos Sara A. , Hatfield Chance E. , Rahman Ryan J. , Consalvo Kristen M. , Dittenhauser Nolan K. , Gomer Richard H. 
Published: June 2023

ABSTRACT
During developmental and immune responses, cells move towards or away from some signals. Although much is known about chemoattraction, chemorepulsion (the movement of cells away from a stimulus) remains poorly understood. Proliferating Dictyostelium discoideum cells secrete a chemorepellent protein called AprA. Examining existing knockout strains, we previously identified proteins required for AprA-induced chemorepulsion, and a genetic screen suggested that the enzyme phosphatidylinositol phosphate kinase A (PIPkinA, also known as Pik6) might also be needed for chemorepulsion. Here, we show that cells lacking PIPkinA are not repelled by AprA, and that this phenotype is rescued by expression of PIPkinA. To bias cell movement, AprA inhibits Ras activation at the side of the cell closest to the source of AprA, and we find that PIPkinA is required for AprA to inhibit Ras activation. PIPkinA decreases levels of phosphatidylinositol 4-phosphate [PI(4)P] and phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3], and possibly because of these effects, potentiates phagocytosis and inhibits cell proliferation. Cells lacking PIPkinA show normal AprA binding, suggesting that PIPkinA regulates chemorepulsion at a step between the AprA receptor and AprA inhibition of Ras activation.
The cytoplasmic tail of the mechanosensitive channel Pkd2 regulates its internalization and clustering in eisosomes
Authors: Malla Mamata , Sinha Debatrayee , Chowdhury Pritha , Bisesi Benjamin Thomas , Chen Qian 
Published: June 2023

ABSTRACT
Polycystins are a family of conserved ion channels, mutations of which lead to one of the most common human genetic disorders, namely, autosomal dominant polycystic kidney disease. Schizosacchromyces pombe possesses an essential polycystin homologue, Pkd2, which directs Ca2+ influx on the cell surface in response to membrane tension, but its structure remains unsolved. Here, we analyzed the structure–function relationship of Pkd2 based on its AlphaFold-predicted structure. Pkd2 consists of three domains, the extracellular lipid-binding domain (LBD), nine-helix transmembrane domain (TMD) and C-terminal cytoplasmic domain (CCD). Our genetic and microscopy data revealed that LBD and TMD are essential for targeting Pkd2 to the plasma membrane from the endoplasmic reticulum. In comparison, CCD ensures the polarized distribution of Pkd2 by promoting its internalization and preventing its clustering in the eisosome, a caveolae-like membrane compartment. The domains of Pkd2 and their functions are conserved in other fission yeast species. We conclude that both extracellular and cytoplasmic domains of Pkd2 are crucial for its intracellular trafficking and function. We propose that mechanosensitive channels can be desensitized through either internalization or clustering in low-tension membrane compartments.
Case Report: Right atrial organized thrombus three years after tricuspid annuloplasty
Authors: Abbass Mohannad , Mariani Silvia , Musa Sami , Erba Nicoletta , Masini Franco , Lentini Salvatore 
Published: June 2023

Background: Occurrence of right atrial masses, especially in patients with history of cardiac surgery, is rare. Differential diagnosis between malignant and non-malignant aetiologies might be cumbersome, and surgery is often required to prevent complications or disease evolution. Case: We report the case of a 16-year-old girl from a rural area of Sudan, who underwent surgery for a modified De Vega’s tricuspid annuloplasty, and mitral and aortic valve replacement with mechanical prostheses. The patient was on regular follow-up but demonstrated a poor compliance to anticoagulation therapy with a time in therapeutic range between 52% and 20%. She remained asymptomatic, but a right atrial mass was diagnosed by transthoracic echocardiography during a follow-up visit 41 months after the first operation. Surgical removal of the mass revealed an organized thrombus arising from the point where the Prolene stitches for the tricuspid annuloplasty were previously passed. The patient recovered from surgery, was discharged home on post-operative day 10 and the first follow-up visit at 30 days after discharge confirmed a good clinical status and a normal transthoracic echocardiography (TTE). Conclusions: This case report describes the diagnostic and therapeutic work-out of a thrombus formation on the suture lines of a tricuspid annuloplasty. Moreover, it highlights the importance of a strict and long follow-up after valvular surgery and of the adherence to anticoagulation therapy, especially for patients living in rural areas of developing countries.
What’s all the chatter about?
Authors: Kunze Kyle N. , Jang Seong J. , Fullerton Mark A. , Vigdorchik Jonathan M. , Haddad Fares S. 
Published: June 2023

The OpenAI chatbot ChatGPT is an artificial intelligence (AI) application that uses state-of-the-art language processing AI. It can perform a vast number of tasks, from writing poetry and explaining complex quantum mechanics, to translating language and writing research articles with a human-like understanding and legitimacy. Since its initial release to the public in November 2022, ChatGPT has garnered considerable attention due to its ability to mimic the patterns of human language, and it has attracted billion-dollar investments from Microsoft and PricewaterhouseCoopers. The scope of ChatGPT and other large language models appears infinite, but there are several important limitations. This editorial provides an introduction to the basic functionality of ChatGPT and other large language models, their current applications and limitations, and the associated implications for clinical practice and research.Cite this article: Bone Joint J 2023;105-B(6):587–589.
Prediction of suitable outpatient candidates following revision total knee arthroplasty using machine learning
Authors: Yeramosu Teja , Ahmad Waleed , Satpathy Jibanananda , Farrar Jacob M. , Golladay Gregory J. , Patel Nirav K. 
Published: June 2023

AimsTo identify variables independently associated with same-day discharge (SDD) of patients following revision total knee arthroplasty (rTKA) and to develop machine learning algorithms to predict suitable candidates for outpatient rTKA.MethodsData were obtained from the American College of Surgeons National Quality Improvement Programme (ACS-NSQIP) database from the years 2018 to 2020. Patients with elective, unilateral rTKA procedures and a total hospital length of stay between zero and four days were included. Demographic, preoperative, and intraoperative variables were analyzed. A multivariable logistic regression (MLR) model and various machine learning techniques were compared using area under the curve (AUC), calibration, and decision curve analysis. Important and significant variables were identified from the models.ResultsOf the 5,600 patients included in this study, 342 (6.1%) underwent SDD. The random forest (RF) model performed the best overall, with an internally validated AUC of 0.810. The ten crucial factors favoring SDD in the RF model include operating time, anaesthesia type, age, BMI, American Society of Anesthesiologists grade, race, history of diabetes, rTKA type, sex, and smoking status. Eight of these variables were also found to be significant in the MLR model.ConclusionThe RF model displayed excellent accuracy and identified clinically important variables for determining candidates for SDD following rTKA. Machine learning techniques such as RF will allow clinicians to accurately risk-stratify their patients preoperatively, in order to optimize resources and improve patient outcomes.Cite this article: Bone Jt Open 2023;4(6):399–407.
High-power distributed feedback lasers based on InP corrugated sidewalls at λ∼2  μm
Authors: Sun Yongqiang , Xu Yunfei , Zhang Jinchuan , Chen Fengmin , Liu Junqi , Liu Shuman , Lu Quanyong , Zhuo Ning , Wang Lijun , Liu Fengqi , Zhai Shenqiang 
Published: May 2023

We report a high-power single-mode InP-based 2 μm distributed feedback (DFB) laser with a second-order buried grating and corrugated sidewalls. A second-order semiconductor grating is used for in-plane feedback and vertical out-coupling. The corrugated sidewalls are used to eliminate higher-order transverse modes. For the DFB laser with a 2 mm long cavity and 15 μm wide ridge, the maximum continuous-wave edge-emitting and surface-emitting single-mode powers at 300 K are up to 81 and 42 mW, respectively. A single-lobed far-field radiation pattern with a low divergence angle of approximately 8.6° is achieved by a device with a ridge width of 15 μm. The single-longitudinal-mode emission wavelength of the fabricated laser can be adjusted from 2003.8 nm at 288 K to 2006.9 nm at 313 K without any mode hopping. Robust single-mode emission with a side-mode suppression ratio of 30 dB is achieved under all injection currents and temperature conditions.
Noise canceled graphene-microcavity fiber laser sensor for ultrasensitive gas detection
Authors: Wang Yuchen , Li Yiwei , Li Yicheng , Zhang Hao , Liu Zihan , Guo Yanhong , Wang Zeping , He Jun , Guo Xuhan , Wang Yiping , Yao Baicheng 
Published: May 2023

Optical microcavities offer a promising platform for highly efficient light–matter interactions. Recently, the combination of microresonators and 2D materials in the nanoscale has further enriched the optoelectronics of microcavity geometries, spurring broad advances including lasers, nonlinear converters, modulators, and sensors. Here, we report the concept of compact dual-laser cogeneration in a graphene-microcavity fiber, which offers a way to cancel the optical common mode noises. Driven by a single 980 nm pump, orthogonally polarized laser lines are generated in a pair of degeneracy breaking modes. The two laser lines produce a heterodyne beat note at 118.96 MHz, with frequency noise down to 200  Hz2/Hz at 1 MHz offset, demonstrating a linewidth of 930 Hz in vacuum. This compact device enables on-line and label-free NH3 gas detection with high resolution, realizing a detection limit on a single pmol/L level, and a capability to quantitatively trace gas–graphene interactions. Such a combination of graphene optoelectronics and microcavity photonics demonstrates a novel physical paradigm for microlaser control and offers a new scheme for in situ chemical sensing.
Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis
Authors: Alshehri Abdullah , Chhonker Yashpal S. , Bala Veenu , Edi Constant , Bjerum Catherine M. , Koudou Benjamin G. , John Lucy N. , Mitjà Oriol , Marks Michael , King Christopher L. , Murry Daryl J. 
Published: June 2023

Background
Ivermectin (IVM) is a broad–spectrum anthelmintic drug used to treat diseases caused by filarial worms, such as onchocerciasis and lymphatic filariasis (LF). IVM is part of a triple–drug therapy used by the Mass Drug Administration (MDA) as a preventive strategy to eradicate LF in sub–Saharan Africa. The drug shows high variability in drug exposure in previous pharmacokinetic studies. This study aims to build a population pharmacokinetic (PopPK) model to identify and quantify the possible sources of the variability of IVM exposure after a single–oral dose in LF–infected subjects and healthy individuals.

Methodology / Principal findings
In this analysis, 724 samples were collected from treatment–naïve Wuchereria bancrofti–infected (n = 32) and uninfected (n = 24) adults living in Côte d’Ivoire who had received one dose of IVM as a part of triple–drug therapy. PopPK analysis was conducted using Phoenix NLME 8.3 software. The Monte Carlo simulation based on the final model was performed to simulate drug exposure among different dosing groups (200 μg/kg, 18 mg, and 36 mg). A two–compartment model with zero–order dose input into the absorption compartment with a lag time function followed by first–order absorption and linear elimination best described the IVM’s pharmacokinetic (PK) parameters. The final model identifies that the PK parameters of IVM are not affected by LF infection. Sex was a significant covariate on the peripheral volume of distribution (Vp/F, 53% lower in men than in women). IVM drug exposure shows linear pharmacokinetic behavior among the simulated dosing groups with similar drug exposure based on sex.

Conclusion/Significance
We have developed a PopPk model to describe and identify possible sources of the variability of IVM exposure. To our knowledge, this is the first PopPK study of IVM in patients with LF.

Trial registration
NCT02845713; NCT03664063
Meta-evaluation of a whole systems programme, ActEarly: A study protocol
Authors: Mansukoski Liina , Lockyer Bridget , Creaser Amy , Sheringham Jessica , Sheard Laura , Garnett Philip , Yang Tiffany , Cookson Richard , Albert Alexandra , Islam Shahid , Shore Robert , Khan Aiysha , Twite Simon , Dawson Tania , Iqbal Halima , Skarda Ieva , Villadsen Aase , Asaria Miqdad , West Jane , Sheldon Trevor , Wright John , Bryant Maria 
Published: June 2023

Introduction
Living in an area with high levels of child poverty predisposes children to poorer mental and physical health. ActEarly is a 5-year research programme that comprises a large number of interventions (>20) with citizen science and co-production embedded. It aims to improve the health and well-being of children and families living in two areas of the UK with high levels of deprivation; Bradford in West Yorkshire, and the London Borough of Tower Hamlets. This protocol outlines the meta-evaluation (an evaluation of evaluations) of the ActEarly programme from a systems perspective, where individual interventions are viewed as events in the wider policy system across the two geographical areas. It includes investigating the programme’s impact on early life health and well-being outcomes, interdisciplinary prevention research collaboration and capacity building, and local and national decision making.

Methods
The ActEarly meta-evaluation will follow and adapt the five iterative stages of the ‘Evaluation of Programmes in Complex Adaptive Systems’ (ENCOMPASS) framework for evaluation of public health programmes in complex adaptive systems. Theory-based and mixed-methods approaches will be used to investigate the fidelity of the ActEarly research programme, and whether, why and how ActEarly contributes to changes in the policy system, and whether alternative explanations can be ruled out. Ripple effects and systems mapping will be used to explore the relationships between interventions and their outcomes, and the degree to which the ActEarly programme encouraged interdisciplinary and prevention research collaboration as intended. A computer simulation model (“LifeSim”) will also be used to evaluate the scale of the potential long-term benefits of cross-sectoral action to tackle the financial, educational and health disadvantages faced by children in Bradford and Tower Hamlets. Together, these approaches will be used to evaluate ActEarly’s dynamic programme outputs at different system levels and measure the programme’s system changes on early life health and well-being.

Discussion
This meta-evaluation protocol presents our plans for using and adapting the ENCOMPASS framework to evaluate the system-wide impact of the early life health and well-being programme, ActEarly. Due to the collaborative and non-linear nature of the work, we reserve the option to change and query some of our evaluation choices based on the feedback we receive from stakeholders to ensure that our evaluation remains relevant and fit for purpose.
Role of wearable devices in cardiac telerehabilitation: A scoping review
Authors: Jones Alexis K. , Yan Crystal Lihong , Rivera Rodriquez Beatriz P. , Kaur Sukhpreet , Andrade-Bucknor Sharon 
Published: May 2023

Background
Cardiac rehabilitation (CR) is an evidence-based comprehensive program that includes exercise training, health education, physical activity promotion, and extensive counseling for the management of cardiovascular risk factors. Wearable devices monitor certain physiological functions, providing biometric data such as heart rate, movement, sleep, ECG analysis, blood pressure, energy expenditure, and numerous other parameters. Recent evidence supports wearable devices as a likely relevant component in cardiovascular risk assessment and disease prevention. The purpose of this scoping review is to better understand the role of wearable devices in home-based CR (HBCR) and to characterize the evidence regarding the incorporation of wearable devices in HBCR programs and cardiovascular outcomes.

Methods & findings
We created a search strategy for multiple databases, including PubMed, Embase (Elsevier), CINAHL (Ebsco), Cochrane CENTRAL (Wiley), and Scopus (Elsevier). Studies were included if the patients were eligible for CR per Medicare guidelines and >18 years of age and if some type of wearable device was utilized during HBCR. Our search yielded 57 studies meeting all criteria. The studies were classified into 4 groups: patients with coronary heart disease (CHD) without heart failure (HF); patients with HF; patients with heart valve repair or replacement; and patients with exposure to center-based CR. In three groups, there was an upward trend toward improvement in quality of life (QOL) and peak VO2, less sedentary time, and an increase in daily step count in the intervention groups compared to control groups.

Conclusions
HBCR using wearable devices can be a comparable alternative or adjunct to center-based CR for patients with CHD and HF. More studies are needed to draw conclusions about the comparability of HBCR to center-based CR in patients with heart valve repair or replacement.