bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Virtual Reality Intervention Programs on the Functionality of Children and Adolescents with Cerebral Palsy. A Systematic Review
Authors: Chrysagis Nikolaos , Panagou Despoina , Erasmia Maria Kouzagioti , Vlachou Efstathia M , Sakellari Vasiliki , Koumantakis George A
Published: July 2023

Background: Cerebral Palsy (CP) is a neurological disorder of movement and posture. Recent studies have shown that Virtual Reality (VR) is a useful and low-cost tool used in treating children and adolescents with cerebral palsy. Nevertheless, there is no substantial evidence supporting that VR therapy can help CP patients, not only as the primary treatment, but as a supplement. Objectives: The present systematic review aimed to investigate the effectiveness of VR intervention programs on the functional capacity of children and adolescents with CP, according to the International Classification of Functioning, Disability and Health (ICF). Methods: A systematic online search was conducted in PubMed, Scopus, and PEDro databases, as well as in the Google Scholar search engine, from inception till September 2022. The methodological quality of included studies was rated with the PEDro scale. Results: Twenty-two randomized-controlled trials were eligible for inclusion. The results indicated that there was a significant improvement after the implementation, of interventional VR programs, in balance and visual perception, while the results were controversial for muscle strength, coordination, gross motor function, gait, upper limb function, independence in activities of Daily Life Activities and participation. Conclusion: Significant balance and visual perception improvements may result from VR programs applied in children and adolescents with CP. Important factors that may influence the results are the functional level of the participants, the sample size, the context in which the therapeutic intervention is carried out (rehabilitation center, home), and the conventional treatments that the VR intervention programs are compared against.
Marginal Fields Development in Nigeria: A Review of Extant Strategies
Authors: Torty C. Kalu-Ulu, , Anietie N. Okon, , Dulu Appah,
Published: July 2023

This paper focuses on the development of marginal fields in Nigeria, the challenges, economic viability, and the role of the government in implementing the contributions of marginal fields to the national oil production output. Also, the previously reported marginal field development and management practices in the Niger Delta oilfield are x-rayed. Following the definition of the marginal field is an overview of different types of marginal field development in the Niger Delta region. Also, the United Kingdom Oil and Gas Recovery Regulatory Commission, the United States Security Exchange Commission, and the Nigerian government's categorization of what compose of a marginal field are included. In addition, the participation of the Nigerian federal government and contributions to the development of marginal fields in the bidding of marginal assets to the development of infrastructure are presented. Particular attention is paid to the factors that affect the development and choice of production strategies in the marginal fields of the Niger Delta. These factors discussed in detail in the document include environmental, technical, social, political, and economic factors. Again, different management and development strategies used by some marginal fields of the Niger Delta are x-rayed and presented with a particular focus on three of those strategies. The three common approaches in the Niger Delta marginal field development strategy are water flooding, infill drilling, and infrastructure sharing. These approaches have made marginal fields in Nigeria operational, competitive, and economically viable to date.
Pemasangan Dan Pembuatan Sistem Monitoring Pada Solar Panel Berkapasitas 450 Wp Di Smp Kristen Petra 2 Surabaya
Authors: Gunawan Cindy Clarisa , Tumbelaka Hanny , . Thiang
Published: July 2023

SMP Kristen Petra 2 adalah SMP swasta yang ada di Surabaya. SMP ini memiliki program sekolah entrepreneur yang mengajarkan bagaimana menghasilkan keuntungan, salah satu caranya dengan menghemat energi yang digunakan. Cara menghemat energi ini bisa dengan menggunakan solar panel. Tidak dipungkiri bahwa pada rangkaian solar panel akan mengalami gangguan jika tidak dilakukan maintenance secara rutin. Maka dari itu dibuatlah sebuah alat yang dapat membaca dan memantau arus dan tegangan yang dapat dipantau dari jarak yang jauh yaitu sebuah sistem monitoring. Sistem ini menggunakan 3 buah sensor dimana terdapat 2 sensor arus dan 1 sensor tegangan. Semua Sensor yang terpasang dikendalikan oleh alat mikrokontroler ESP32. Mikrokontroler ini difungsikan untuk menerima, mengelola dan mengirim data dari pembacaan sensor. Hasil dari pembacaan ditampilkan dalam web dan juga dalam LCD yang telah terpasang. Sebelum memasang sensor dilakukan Pengujian dalam pembacaan sensor dengan melakukan beberapa percobaan yaitu dengan memberikan beberapa macam beban yang berbeda-beda (untuk sensor arus) dan beberapa macam sumber tegangan yang berbeda-beda (untuk sensor tegangan). Hasil yang diperoleh dari percobaan adalah sensor arus memiliki selisih pembacaan 0.5A-0.6A sensor ini tidak dapat membaca arus di bawah 1A. Hasil pengujian sensor tegangan memiliki selisih pembacaan 0.73V sensor ini tidak dapat membaca tegangan dibawah 0.73V.

Kata Kunci: Solar Panel, ESP32, Sensor Tegangan DC, Sensor Arus ACS712, Modul I2C, Buzzer.
Prototipe Robot Pramusaji Untuk Mengantar Makanan
Authors: Edwardo Albryan , . Thiang , Khoswanto Handry
Published: July 2023

Pandemi COVID-19 ini masyarakat dihimbau untuk menjaga jarak dan tidak memperbesar kerumunan. Agar tetap dapat melayani pelanggan namun tidak memberbesar kerumunan dan tetap menjaga jarak, maka dalam penelitian ini dikembangkanlah membuat prototipe robot pramusaji yang dapat mengantarkan makanan dari satu meja ke meja lain menggunakan metode line following. Robot akan berjalan dari dapur ke meja pelanggan dengan mengikuti garis hitam yang terpasang disekitar meja. Dalam sekali pengantaran makanan, robot dapat mengantar makanan ke 2 destinasi meja sekaligus. Hasil dari pengujian ini dapat disimpulkan bahwa robot ini mampu mengantarkan makanan dari dapur atau garasi ke destinasi meja pertama dan meja lain lalu kembali dalam waktu 1,5-2 menit, mampu mendeteksi halangan 8-30 cm dengan baik dengan tingkat keberhasilannya 100%. Namun memiliki kelemahan seperti kesalahan desain line follower yang dipasang ditengah robot sehingga pergerakan robot menjadi kurang baik. Ketika robot berjalan miring dari awal robot berjalan, maka perjalanan selanjutnya akan terus miring dan sulit untuk kembali berjalan lurus.

 

Kata Kunci— Prototipe robot Pramusaji, line following, Arduino Mega 2560.
RANCANG BANGUN SISTEM METER LISTRIK PRABAYAR DENGAN PEMBAYARAN MENGGUNAKAN QRIS DI RUMAH KOST
Authors: Wahanie Gregorio Diovani , Lim Resmana , Sugiarto Indar
Published: July 2023

Pada penelitian ini dikembangkan suatu sistem yang dapat memantau konsumsi listrik dengan metode memasang meter listrik digital berbasis mikrokontroler. Tidak seperti kWh Meter Prabayar PLN yang Offline, namun meter prabayar ini terhubung dengan internet/Online sehingga tidak memerlukan motode token,  dan dapat dimonitor dan top-up pulsa listrik dapat dilakukan langsung secara online. Sistem ini nantinya akan terintergasi secara online melalui aplikasi payment gateway untuk keperluan transaksi secara non-tunai. Sistem ini terdiri dari mikrokontroler ESP32, bagian output terdiri dari LCD 16x2, buzzer, SSR dan LED, dan bagian input terdapat sensor PZEM untuk mengukur energi listrik yang digunakan. Sistem ini juga dapat dimonitor secara internet berbasis web. Hasil Pengujian akurasi pengukuran energi PZEM dengan modul pembanding sejenis SDM120 secara pembacaan dan Analisa matematis menujukan parameter yang mendekati sama. Pengujian pengisian pulsa berhasil melakukan pengisian ulang pulsa listrik sebesar 1 kWh dengan tarif yang dipasang sebesar Rp 1500,- per kWh. Web dashboard yang dikembangkan telah menunjukan hasil fungsi monitoring dan report dari sistem meteran yang dibuat.
Association of State Funding for Comprehensive Reproductive Health Care With Use of Contraception Among Latina Patients and Non-Latina Patients in Oregon
Authors: Cohen Megan A. , Boniface Emily R. , Skye Megan , Linz Rachel , Pedhiwala Nisreen , Rodriguez Maria I.
Published: July 2023

Importance

There are well-documented racial and ethnic disparities in effective contraceptive use due to multiple factors. A key contributor may be differential insurance coverage and patient costs. The Oregon Reproductive Health Equity Act (RHEA), enacted in 2017, ensures full coverage of reproductive health care without cost sharing for all Oregonians with low income.

Objective

To assess whether removing financial barriers to accessing contraceptive care is associated with an improvement in use of moderately and highly effective contraceptive methods among Latina women compared with non-Latina women.

Design, Setting, and Participants

This cohort study included women aged 12 to 51 years who sought contraceptive care in the Oregon Health Authority Reproductive Health Program from April 2016 to March 2020. Patients using permanent contraception, those missing data on ethnicity, and non-Oregon residents were excluded. Data analysis was performed in January 2021.

Exposures

Contraceptive care in the Reproductive Health Program after RHEA implementation.

Main Outcomes and Measures

The main outcome was prevalence of use of moderately effective methods (contraceptive pills, patch, ring, or injection) or highly effective methods (long-acting reversible contraceptives) at the time of the contraceptive visit. Difference-in-differences analysis was used to compare moderately and highly effective contraception use between Latina and non-Latina patients. Secondary outcomes were proportions of adoption or continuation of moderately and highly effective methods, prevalence of highly effective methods, and adoption or continuation of highly effective methods. The unit of analysis was at the clinic visit level.

Results

The study sample consisted of 295 604 evaluable clinic visits, in which 28.4% of individuals identified as Latina and 71.6% of individuals identified as non-Latina. The mean (SD) age was 25.5 (8.1) years. With difference-in-differences analysis, there was a significant adjusted 1.9 percentage point (95% CI, 0.2-3.6 percentage points) increase in prevalence of moderately or highly effective contraceptive methods for Latina patients compared with non-Latina patients. There were no significant differences for other outcomes of interest.

Conclusions

This cohort study found that in Oregon, legislation removing financial barriers to accessing contraceptive care was associated with significant mitigation in disparate moderately and highly effective contraceptive method prevalence for Latina patients compared with non-Latina patients. The findings suggest that state funds successfully supplanted federal funds to enable continued robust comprehensive family planning services after withdrawal from Title X.
Authority of Medicare to Limit Coverage of FDA-Approved Products
Authors: Daval C. Joseph Ross , Kesselheim Aaron S.
Published: July 2023

Importance

When the US Food and Drug Administration (FDA) approves a drug or medical device on the basis of limited clinical evidence, the Centers for Medicare & Medicaid Services (CMS) must decide whether the therapy is “reasonable and necessary” for coverage among Medicare beneficiaries. However, the legal underpinnings of CMS’s authority to shape coverage of FDA-regulated products under Medicare Part B are controversial. To clarify this area, we reviewed relevant legal precedents on CMS’s approaches to limit coverage and recent decisions Medicare has issued affecting coverage for FDA-regulated products.

Observations

The CMS continues to exercise considerable legal discretion to limit coverage of FDA-authorized products to only uses it determines are reasonable and necessary for patients with Medicare. Courts have upheld this discretion repeatedly, emphasizing the difference between Medicare’s coverage criteria and the FDA’s review standards. As more new drugs and devices come to market without solid evidence of efficacy on clinical outcomes, or have narrow benefit-risk considerations, CMS may increasingly rely on forms of limited or conditional coverage, including coverage with evidence development (CED), which provides reimbursement only in the context of a clinical trial or registry.

Conclusions and Relevance

The ability of CMS to condition or limit coverage of FDA-approved products is a commonsense necessity for this crucial taxpayer-funded program. Although courts have thus far deferred to the authority of CMS to make such decisions on the basis of its clear statutory discretion and public health expertise, Congress may want to act to reaffirm statutory language giving CMS sufficient flexibility to craft coverage determinations that reflect the evidence for a product’s use.
What Parents Should Know About Bugs and Bug Repellents
Authors: Henderson Emily J. , Rutt Jennifer N. , Albertini Laurie W.
Published: July 2023

This Patient Page describes how to protect children against insect bites, how to choose a bug repellent, and tips for applying bug repellent.
Nuclear Transfer from Cell Lines
Authors: Wakayama Sayaka , Wakayama Teruhiko , Wells David N
Published: July 2023

The production of cloned animals following nuclear transfer, using somatic cells grown in culture, represents a remarkable feat of developmental biology. It demonstrates the potential of a differentiated nucleus to be reprogrammed back to an embryonic state when exposed to a suitable cytoplasmic environment, such as that of an enucleated oocyte. It involves fundamental changes to the patterns of DNA methylation and chromatin modification imposed on a specialised nucleus to enable the precise temporal‐spatial sequence of gene expression necessary for normal embryogenesis. However, reprogramming is often incomplete with development going astray, resulting in a continuum of embryo, fetal and postnatal mortality. The majority of the clones that do survive to adulthood, and their sexually derived progeny, do, however, appear normal. This provides encouragement for the practical applications of nuclear cloning in the fields of agriculture, animal conservation and biomedicine.

Key Concepts

The cytoplasm of mature oocytes has the potential to reprogramme the epigenetic state and pattern of gene expression of differentiated donor cells back to that of an embryo following nuclear transfer, enabling the production of cloned animals.

The success rate of cloned animals is more influenced by differences in nuclear transfer method than by the type of animal or cell.

Because cultured cells can be multiplied, cryopreserved, andused at any time, cloning animals from cultured cells has many advantages overusing fresh cells collected from animals.

Using nuclear transfer technology, embryonic stem (ES) cell lines can be generated from somatic cells, and cloned animals can be produced using these cultured cells as donors.

Epigenetic abnormalities frequently occur in cloned animals, but the next generation born from the cloned parents are normal and can be used without problems in livestock production.

Cloning technology could help save endangered species.
Genetics of Cutis Laxa
Authors: Beyens Aude , Callewaert Bert
Published: July 2023

Cutis laxa syndromes are a heterogeneous group of multisystem disorders with prominent connective tissue features including loose redundant skin folds, a clinical hallmark shared among all subtypes. The skin laxity results from severe dermal elastic fibre fragmentation. The molecular defects underlying congenital forms of cutis laxa may affect any step in elastic fibre assembly, as illustrated by the identification of pathogenic variants in different extracellular matrix proteins, including elastin, latent transforming growth factor β proteins and fibulins (
ELN
,
LTBP4
,
FBLN4
,
FBLN5, LOX, EMILIN1, LTPB1
), cellular trafficking (
ATP6V0A2, ATP6V1E1, ATP6V1A
and
ATP7A
) and metabolic processes (
ALDH18A1, PYCR1)
. The latter two groups have been referred to as neurometabolic cutis laxa and may present with skeletal and neurological phenotypes in addition to connective tissue manifestations.

Key Concepts

Elastic fibres (EF) provide resilience and elasticity to the connective tissue and contribute to tissue homeostasis by regulating cytokine signalling and cell–matrix interactions.

Elastic fibre synthesis or elastogenesis is a complex spatiotemporally regulated multistep process.

Cutis laxa syndromes are a heterogeneous group of multisystem connective tissue disorders that share loose redundant skin folds, that vary significantly in severity and spectrum of the associated clinical manifestations.

The molecular defects underlying congenital forms of cutis laxa involve all steps in EF synthesis, affecting different extracellular matrix proteins (
ELN, LTBP4, FBLN4, FBLN5, LOX, EMILIN1, LTBP1
), cellular trafficking (
ATP6V0A2, ATP6V1E1, ATP6V1A, SCYL1BP1 and ATP7A
) and metabolism (
ALDH18A1, PYCR1
).

Cutis laxa caused by defects in extracellular matrix proteins present with prominent arterial and/or pulmonary abnormalities.

Cutis laxa caused by intracellular trafficking disorders and/or metabolic disorders may present with intellectual deficiency, skeletal and/or ocular defects.
Genetics of Motor Neuron Diseases
Authors: Chaudhary Rishabh , Mishra Vikas
Published: July 2023

Motor neuron diseases, also known as MNDs, are a group of extremely severe neurological conditions that, in most cases, result in death. These diseases are primarily characterised by the gradual degeneration and/or loss of motor neurons in the brainstem and spinal cord regions. Genetic mutations are one of the main triggers of MND pathogenesis, and researchers have identified more than 100 different genes in humans that have been altered. Previous studies have shown that many of the enzymatic transcriptional products produced by the defective or mutated genes that cause MNDs are involved in the dysregulation of several key intracellular and molecular pathways that are essential for proper motor neuron functioning. These include RNA transport and splicing, protein homeostasis, microglial cell activation, mitochondrial functions, axonal protein transport, protein folding and many more.

Key Concepts

Motor neuron disease is a fatal neurodegenerative condition that affects motor neurons in the central nervous system.

Genetic factors play a major role in the initiation and progression of motor neuron disease.

Over the past few years, hundreds of genes that play causative roles in motor neuron disorders have been discovered.

Identifying novel genes or rare genetic variants involved in motor neuron disease pathophysiology is extremely vital.

The use of various high‐throughput gene sequencing techniques has been shown to be an effective tool for discovering genes related to motor neuron diseases.

Alterations in the expression of genes in motor neuron disease cause dysregulation of several intracellular pathways that are essential for healthy motoneuron functioning.

The mechanism underlying the death of motor neurons is influenced by a number of different cellular and molecular processes.

Toxic gain‐of‐function or loss‐of‐function of a specific protein causes abnormalities in synapse mechanisms, which leads to the degeneration or death of motor neurons.

Even though the first case of motor neuron disease was documented more than a century ago, there is still no effective treatment or a viable cure available for the disease.

At present, managing disease symptoms and providing palliative care are still the main goals of motor neuron disease therapy.
Interpretation of Variants in Clinical Genomics
Authors: Jackson Maria , Stobo Daniel
Published: July 2023

Many health conditions are genetic in origin, and it is often necessary to identify the causative DNA variant(s) in the patient in order to confirm a potential genetic diagnosis, so that optimal management and/or treatment can be implemented. This process can be complicated by the massive amount of variation present in all our genomes, so that distinguishing pathogenic variants from benign ones can be challenging. In order to provide consistency and improved validity of interpretations from different diagnostic laboratories across the world, professional guidelines have recently been published which specify how various types of evidence from scientific literature, databases, functional studies and
in silico
analysis should be combined to generate a classification for a variant. Ongoing work seeks to improve these guidelines, including the generation of versions specific for particular conditions and specific guidelines for classification of copy number variants and somatic variants.

Key Concepts

Analysis of patient DNA to identify pathogenic variants is often a critical step in confirming a genetic diagnosis.

Most of the variants found in any human genome are benign, so clinical scientists need to be able to identify which are (likely) pathogenic.

Other reports of a variant, in scientific literature or databases, and/or reports from functional assays can help to classify variants as (likely) benign or (likely) pathogenic.

Computer software can be used to conduct
in silico
analysis to predict potential pathogenicity of a variant.

Professional guidelines have been generated for combining different types of evidence during variant interpretation, and these are used internationally, to ensure consistent outcomes in variant interpretation, both in general use and for specific genetic conditions.

Despite careful evaluation according to the guidelines, many variants identified in patient DNA remain as variants of uncertain significance (VUS) due to insufficient or contradictory evidence.
Self‐Fertilising Populations and Adaptation
Authors: Clo Josselin
Published: July 2023

The evolution to self‐fertilisation from outcrossing is one of the most frequent transitions in mating strategies. Recurrent self‐fertilisation, and inbreeding in general, is thought to lead to a reduction in adaptive capacities, thus leading selfing lineages down an evolutionary ‘blind alley’. A centenary of empirical and theoretical research studied in which conditions the evolution of self‐fertilisation is associated with a reduction in adaptive potential, notably when adaptation occurs thanks to
de novo
mutations and standing genetic diversity. Recent results suggest that adaptation from de novo mutations is less likely in selfing populations compared to outcrossing ones, while adaptation from standing genetic diversity is at least as likely.

Key Concepts

Adaptation from
de novo
mutations is limited in self‐fertilising populations because of selective interference at other loci.

The quantitative genetics of inbred populations is complex because of the joint inheritance of additive and dominance variances.

Recent models and meta‐analyses have shown that self‐fertilisation does not lead to a reduction of the heritable genetic diversity.

Self‐fertilization is ubiquitous in plants and animals kingdoms, with 70% of angiosperm species self‐fertilizing to some extent.

Self‐fertilization is often described as an evolutionary dead‐end, notably due to limited capacities to adapt to new environmental conditions.
Companion Cell and Sieve Elements
Authors: Kim Ji‐Yun , Frommer Wolf B
Published: July 2023

Companion cells and sieve elements are two cell types that are key components of the phloem – a tissue responsible for the translocation of inorganic and organic compounds as well as signals from the leaves to the sites of use. Companion cells form a functional unit with the sieve elements for long‐distance translocation of assimilates, nutrients and signalling molecules and play indispensable roles throughout the life cycle of plants.

Key Concepts

Sieve elements are cells specialised in translocation of phloem sap.

Sieve elements degrade their nucleus and other organelles during development to produce a conduit

Enucleate sieve elements are kept alive by the tightly connected companion cells.

Plasmodesmata connect companion cells and sieve elements, likely to provide conduits for the exchange of ions, metabolites, hormones, RNAs and proteins.

The sieve element companion cell complex is specialised in phloem loading, in the case of sucrose via SUT sucrose/H
+
symporters, in the case of amino acids via AAP amino acid/H
+
symporters.

Other specialised forms of companion cells include transfer cells and intermediary cells, characterised either by increased plasma membrane surface due to reticulate cell wall invaginations or specialised metabolism for raffinose translocation.

Companion cells play crucial roles in hosting diverse metabolic and signalling processes.
Phenotypic and Developmental Plasticity in Plants
Authors: Bush Susan M
Published: July 2023

Plants have a remarkable ability to alter their development in response to a multitude of environmental cues or stressors. This phenotypic plasticity allows them to continually adapt to their local environment, a necessity for plants as immobile, sessile organisms. A host of environmental cues can be interpreted by plants, including light, temperature, water, and nutrient levels, and these inputs are integrated and translated into a range of developmental outputs from shoot elongation, regulation of root gravitropism, altered flowering time, timing of germination, and overall plant yield. Plasticity enables growth optimisation for a plant's local environment, allows expansion of a species' range into heterogeneous habitats, and may provide an advantage as the changing climate affects growth conditions around the globe. Studies in the model organism
Arabidopsis thaliana
, as well as in economically important crop plants like tomato and wheat, are helping to more thoroughly define molecular mechanisms for plastic growth responses. Moving forward, studies of growth and plasticity of plants under multiple, integrated stress conditions will help expand our knowledge and abilities to grow crops in a changing climate and feed our ever‐expanding population.

Key Concepts

Phenotypic plasticity is the ability of a single genotype to produce a range of phenotypes in response to different environmental conditions.

The type and degree of a plant's developmental plasticity will help determine future success of individuals and species in changing climates or altered habitats.

Multiple environmental signals are integrated to regulate plant growth, development, and yield.

Developmental plasticity comes from the meristem, which continuously produces organs throughout the plant's life cycle.

Environmental cues can lead to changes in a plant's gene expression and protein abundance, phytohormone‐responsive signalling, and also epigenetic modifications to the plant's genome.

Natural genetic variation within a plant species can confer variable plasticity of development in response to a single abiotic stressor, causing some varieties of plants to be hardier than others.
Floral Meristems
Authors: Schneitz Kay , Mukherjee Sourav , Balasubramanian Sureshkumar
Published: July 2023

Meristems refer to a group of undifferentiated dividing cells that are responsible for the formation of plant organs. Floral meristems are a group of dividing cells that give rise to flowers. The formation of a floral meristem and its subsequent fate are under both environmental and molecular control. Several exogenous environmental factors and a complex network of genes control this process.

Key Concepts

Meristems refer to a group of undifferentiated dividing cells that form diverse plant organs.

Shoot and root apical meristems give raise to above‐ground and below‐ground plant organs.

Shoot apical meristem produces leaves at its flanks in the vegetative state and flowers in the reproductive state.

Floral meristems are a group of dividing cells that give rise to flowers.

The formation of a floral meristem and its subsequent fate are under both environmental and molecular control.

Several exogenous environmental factors and a complex network of genes control this process.
Medicinal Cannabis Use for Rheumatic Conditions in the US Versus Canada: Rationale for Use and Patient–Health Care Provider Interactions
Authors: Boehnke Kevin F. , Martel Marc O. , Smith Tristin , He Ying , Bergmans Rachel S. , Kruger Daniel J. , Andwele Michele , Bevan Sian , Williams David A. , Fitzcharles Mary‐Ann
Published: July 2023

Objective

Understanding how medical cannabis (MC) use is integrated into medical practice for rheumatic disease management is essential. We characterized rationale for MC use, patient–physician interactions around MC, and MC use patterns among people with rheumatic conditions in the US and Canada.

Methods

We surveyed 3406 participants with rheumatic conditions in the US and Canada, with 1727 completing the survey (50.7% response rate). We assessed disclosure of MC use to health care providers, MC authorization by health care providers, and MC use patterns and investigated factors associated with MC disclosure to health care providers in the US versus Canada.

Results

Overall, 54.9% of US respondents and 78.0% of Canadians reported past or current MC use, typically because of inadequate symptom relief from other medications. Compared to those in Canada, fewer US participants obtained MC licenses, disclosed MC use to their health care providers, or asked advice on how to use MC (all P values <0.001). Overall, 47.4% of Canadian versus 28.2% of US participants rated their medical professionals as their most trusted information source. MC legality in state of residence was associated with 2.49 greater odds of disclosing MC use to health care providers (95% confidence interval: 1.49‐4.16, P < 0.001) in the US, whereas there were no factors associated with MC disclosure in Canada. Our study is limited by our convenience sampling strategy and cross‐sectional design.

Conclusion

Despite widespread availability, MC is poorly integrated into rheumatic disease care, with most patients self‐directing use with minimal or no clinical oversight. Concerted efforts to integrate MC into education and clinical policy is critical.
Adaptive state observation of linear time‐varying systems with switching unknown parameters: Application to gain scheduling and event‐triggered control
Authors: Romero Jose Guadalupe , Ortega Romeo
Published: July 2023

Motivated by its application in gain scheduling and event‐triggered controllers we propose in this paper an adaptive observer for linear time‐varying (LTV) systems with unknown switching parameters, but known switching time instants. To construct the observer we propose an extension to the generalized parameter estimation‐based observers (GPEBO), which we combine with the least‐squares plus dynamic regression extension and mixing (LS+DREM) estimator recently proposed. We prove that the system state and the parameters converge infinite timeinside each switching sub‐interval, under the weak assumption of interval‐excitation (IE). The excellent performance of the proposed observer is illustrated with a practical and an academic example both reported in the literature.
After 15 years, parity enforcement bolstered with new rules
Authors: Knopf Alison
Published: July 2023

The Mental Health Parity and Addiction Equity Act (MHPAEA), a victory for substance use disorder (SUD) patients and providers, was enacted as part of the bank bailout law in 2008 (see https://onlinelibrary.wiley.com/doi/epdf/10.1002/adaw.20157). Going full steam ahead, the MHPAEA quickly righted some of the wrongs, by making certain limitations the same for behavioral (SUD and mental health) conditions as they were for medical/surgical conditions. However, a major disappointment took place when the Obama administration decided that enforcement would be left up to the states, not the federal government (see https://onlinelibrary.wiley.com/doi/epdf/10.1002/adaw.20301).
Biohybrid Hydrogels for Tumoroid Culture
Authors: Castellote‐Borrell Miquel , Merlina Francesca , Rodríguez Adrián R. , Guasch Judith
Published: July 2023

Tumoroids are 3D in vitro models that recapitulate key features of in vivo tumors, such as their architecture — hypoxic center and oxygenated outer layer — in contrast with traditional 2D cell cultures. Moreover, they may be able to preserve the patient‐specific signature in terms of cell heterogeneity and mutations. Tumoroids are, therefore, interesting tools for improving the understanding of cancer biology, developing new drugs, and potentially designing personalized therapeutic plans. Currently, tumoroids are most often established using basement membrane extracts (BME), which provide a multitude of biological cues. However, BME are characterized by a lack of well‐defined composition, limited reproducibility, and potential immunogenicity as a consequence of their natural origin. Synthetic polymers can overcome these problems but lack structural and biochemical complexity, which can limit the functional capabilities of organoids. Biohybrid hydrogels consisting of both natural and synthetic components can combine their advantages and offer superior 3D culture systems. In this review, it is summarized efforts devoted to producing tumoroids using different types of biohybrid hydrogels, which are classified according to their crosslinking mechanism.
Construction and Validation of a Prognostic Model Based on Novel Senescence‐Related Genes in Non‐Small Cell Lung Cancer Patients with Drug Sensitivity and Tumor Microenvironment
Authors: Liu Xiwen , Lin Lixuan , Cai Qi , Sheng Hongxu , Zeng Ruiqi , Zhao Yi , Qiu Xinyi , Liu Huiting , Huang Linchong , Liang Wenhua , He Jianxing
Published: July 2023

Cellular senescence contributes to cancer pathogenesis and immune regulation. Using the LASSO Cox regression, we developed a 12‐gene prognostic signature for lung adenocarcinoma (LUAD) from The Cancer Genome Atlas (TCGA) and a Gene Expression Omnibus (GEO) dataset. We assessed gene expression, drug sensitivity, immune infiltration, and conducted cell line experiments. High‐risk LUAD patients showed increased mortality risk and shorter survival (P < 0.001). Senescence‐related gene analysis indicated differences in protein phosphorylation and DNA methylation between normal individuals and LUAD patients. The high‐risk group showed a positive association with PD‐L1 expression (P = 0.003). Single‐cell sequencing data suggested PEBP1 might significantly impact T cell infiltration. We predicted potential sensitive compounds for 12 senescence genes and found GAPDH promoted cell line proliferation. We established a novel prognostic system based on a newly identified senescence gene. High‐risk patients had elevated immunosuppressive markers, and PEBP1 might influence T cell infiltration significantly. GAPDH, expressed at higher levels in tumors, could affect cancer progression. Our drug prediction model may guide treatment selection.
Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery
Authors: Attia Lucas , Chen Liang‐Hsun , Doyle Patrick S.
Published: July 2023

Hydrophobic active pharmaceutical ingredients (APIs) are ubiquitous in the drug development pipeline, but their poor bioavailability often prevents their translation into drug products. Industrial processes to formulate hydrophobic APIs are expensive, difficult to optimize, and not flexible enough to incorporate customizable drug release profiles into drug products. Here, a novel, dual‐responsive gelation process that exploits orthogonal thermo‐responsive and ion‐responsive gelations is introduced. This one‐step “dual gelation” synthesizes core–shell (methylcellulose‐alginate) hydrogel particles and encapsulates drug‐laden nanoemulsions in the hydrogel matrices. In situ crystallization templates drug nanocrystals inside the polymeric core, while a kinetically stable amorphous solid dispersion is templated in the shell. Drug release is explored as a function of particle geometry, and programmable release is demonstrated for various therapeutic applications including delayed pulsatile release and sequential release of a model fixed‐dose combination drug product of ibuprofen and fenofibrate. Independent control over drug loading between the shell and the core is demonstrated. This formulation approach is shown to be a flexible process to develop drug products with biocompatible materials, facile synthesis, and precise drug release performance. This work suggests and applies a novel method to leverage orthogonal gel chemistries to generate functional core–shell hydrogel particles.
Emerging Advances of Liquid Metal toward Flexible Sensors
Authors: Qin Jinghan , Cui Dandan , Ren Long , Hao Weichang , Shi Yan , Du Yi
Published: July 2023

With the rising demand for biosignal detection, many wearable sensors emerge in recent years. Such a new generation of sensors relies on major breakthroughs in soft sensing materials, which can be bent, compressed, and stretched in a large range. Ga‐based liquid metals (LM) offer a unique combination of high deformability, electrical conductivity, and biocompatibility, making them ideal functional candidate materials for wearable sensors. Numerous studies design various LM sensors for detecting and modulating diverse signals. Nevertheless, further systematic discussion is still missing regarding their operational mechanism, structure defects, and potential solutions. In this review, recent progress in the application of Ga‐based LM sensors is summarized and discussed, with a focus on the sensing principles corresponding to distinct LM properties, the problems, and solutions to each type of sensor. The key challenges toward biosignal detection and future research orientations are discussed.
Tuning Phase Purity in Chiral 2D Perovskites
Authors: Scalon Lucas , Brunner Julius , Guaita Maria Gabriella Detone , Szostak Rodrigo , Albaladejo‐Siguan Miguel , Kodalle Tim , Guerrero‐León L. Andrés , Sutter‐Fella Carolin M. , Oliveira Caio C. , Vaynzof Yana , Nogueira Ana Flavia
Published: July 2023

The introduction of chiral organic spacers in low‐dimensional metal‐halide perovskites triggers chiroptical activity, which is appealing for spintronic applications. However, a comprehensive understanding of structure formation and the ability to control phase purity in such materials have yet to be developed. Herein, the impact of processing conditions on the phase purity, microstructure, and chiroptical properties of chiral 2D perovskites is explored. The anisotropic emergence of a 1D perovskite inside the 2D matrix and its dependence on the organic cation chirality, solvent, and thermal annealing conditions are shown. By controlling these parameters, the in‐plane conductivity of the films is nearly doubled. Furthermore, it is demonstrated, for the first time, that solvent choice and the spatial configuration of the organic cation can have an impact on the residual lattice strain and the energetic disorder of the system. The fundamentals presented here can help to improve the film deposition methods for low‐dimensional chiral perovskites, offering strategies to control phase purity.
Monolithically Integrated BiVO4/Si Tandem Devices Enabling Unbiased Photoelectrochemical Water Splitting
Authors: Jung Gihun , Moon Choongman , Martinho Filipe , Jung Yonghoon , Chu Jinwoo , Park Hyewon , Hajijafarassar Alireza , Nielsen Rasmus , Schou Jørgen , Park Jeongyoung , Vesborg Peter Christian Kjærgaard , Hansen Ole , Lee Yun Seog , Canulescu Stela , Shin Byungha
Published: July 2023

A photoelectrochemical (PEC) water splitting device based on a dual‐junction monolithic tandem cell that utilizes NiOOH/FeOOH/BiVO4/SnO2/Ta:SnO2 (TTO)/tunnel oxide passivated contact (TOPCon) Si is reported. The PEC device achieves a maximum photocurrent density of 1.4 mA cm−2 (equal to a solar‐to‐hydrogen conversion efficiency of 1.72%) in 1.0 m potassium borate solution (pH 9) when illuminated with air mass 1.5 G simulated solar irradiation, which is the highest value among dual‐junction monolithic photoelectrochemical cells except for III–V materials. The TOPCon Si not only works as an appropriate bottom photoelectrode for subsequent high‐temperature BiVO4 processing but also offers a high photovoltage of 590 mV. Transparent and conductive TTO grown by pulsed laser deposition serves as a recombination layer to achieve effective integration. In addition, the TTO provides chemical and physical protection, allowing the surface of the TOPCon Si to exhibit 24 h of tandem cell stability under weak base electrolyte conditions. The SnO2 hole‐blocking layer inserted between TTO and BiVO4 enhances the charge separation of BiVO4, allowing the device to achieve high efficiency. Artificial leaf‐type monolithic tandem cells consisting of NiFe/BiVO4/SnO2/TTO/TOPCon Si/Ag/Ti/Pt with a solar‐to‐hydrogen efficiency of 0.44% are also demonstrated.
Silk Fibroin Particles as Carriers in the Development of Hemoglobin‐Based Oxygen Carriers
Authors: Pacheco Marisa O. , Lutz Henry M. , Armada Jostin , Davies Nickolas , Gerzenshtein Isabelle K. , Cakley Alaura S. , Spiess Bruce D. , Stoppel Whitney L.
Published: July 2023

Oxygen therapeutics has a range of applications in transfusion medicine and disease treatment. Synthetic molecules and all‐natural or semisynthetic hemoglobin‐based oxygen carriers (HBOCs) have seen success as potential circulating oxygen carriers. However, many early HBOC products stalled in development due to side effects from excess hemoglobin in the blood stream and hemoglobin entering the tissue. To overcome these issues, research has focused on increasing the molecular diameter of hemoglobin by polymerizing hemoglobin molecules or encapsulating hemoglobin in liposomal carriers. This work leverages the properties of silk fibroin, a cytocompatible and nonthrombogenic biopolymer, known to entrap protein‐based cargo, to engineer a fully protein‐based oxygen carrier. Herein, an all‐aqueous solvent evaporation technique is used to form silk particles via phase separation from a bulk polyvinyl alcohol phase. Particle size is tuned, and particles are formed with and without hemoglobin. The encapsulation efficiency and ferrous state of hemoglobin are analyzed, resulting in 60% encapsulation efficiency and a maximum of 20% ferric hemoglobin, yielding 100 μg mL−1 active hemoglobin in certain silk fibroin‐HBOCs formulations. The system does not elicit a strong inflammation response in vitro, demonstrating the potential for this particle system to serve as an injectable HBOC.
Validation of the Numen Field by the Energy Conditions in the Early Universe
Authors: Melia Fulvio
Published: July 2023

The energy conditions in general relativity are introduced to establish powerful theorems without having to restrict their applicability to specific choices of the stress‐energy tensor. They are famously invoked, e.g., to prove the singularity theorems of Penrose and Hawking, but have also been applied elsewhere, including various tests of certain cosmological theories. These conditions have become somewhat controversial, however, because they appear to be violated by commonly accepted scenarios, such as inflation shortly after the Big Bang and late‐time acceleration of the cosmic expansion. But accommodating these processes by abandoning all of the energy conditions will promote other disquieting possibilities, including the breakdown of causality with traversable wormholes and closed timeloops. This paper advocates for the opposite viewpoint, demonstrating that the ‘numen’ scalar field, derived from the zero active mass condition in general relativity, satisfies all of the energy conditions in the early Universe. This unique feature among scalar fields adds to its success in accounting for the observed properties of the cosmic microwave background better than its inflationary counterpart. Specifically, numen's complete consistency with all of the energy conditions, and inflation's violation of at least one of them, provides additional justification for theoretically favoring the former over the latter.
Stabilizing Pt Single Atoms through Pt−Se Electron Bridges on Vacancy‐enriched Nickel Selenide for Efficient Electrocatalytic Hydrogen Evolution
Authors: Chen Zanyu , Li Xiaopeng , Zhao Jun , Zhang Shiyu , Wang Jiajun , Zhang Hong , Zhang Jinfeng , Dong Qiujiang , Zhang Wanxing , Hu Wenbin , Han Xiaopeng
Published: July 2023

Rational design of Pt single‐atom catalysts provides a promising strategy to significantly improve the electrocatalytic activity for hydrogen evolution reaction. In this work, we presented a novel and efficient strategy for utilizing the low electron‐density region of substrate to effectively trap and confine high electron‐density metal atoms. The Pt single‐atom catalyst supported by nickel selenide with rich vacancies was prepared via a hydrothermal‐impregnation stepwise approach. Through experimental testation and DFT theoretical calculation, we confirm that Pt single atoms are well distributed at cationic vacancies of nickel selenide with loading amount of 3.2 wt. %. Moreover, the atomic Pt combined with the high electronegative Se to form Pt−Se bond as a “bridge” between single atoms and substrate for fast electron translation. This novel catalyst shows an extremely low overpotential of 45 mV at 10 mA cm−2 and an excellent stability over 120 h. Furthermore, the nickel selenide supported Pt SACs exhibits long‐term stability for practical application, which maintains a high current density of 390 mA cm−2 over 80 h with a retention of 99 %. This work points a promising direction for designing single atoms catalysts with high catalytic activity and stability for advanced green energy conversion technologies.
Using Aggregation to Chaperone Nanoparticles Across Fluid Interfaces
Authors: Fu Yuchen , Zhao Sai , Fan Yulong , Ho Yannis Yan Lum , Wang Yufeng , Lei Dangyuan , Gu Peiyang , Russell Thomas P. , Chai Yu
Published: July 2023

Nanoparticles (NPs) transfer is usually induced by adding ligands to modify NP surfaces, but aggregation of NPs oftentimes hampers the transfer. Here, we show that aggregation during NP phase transfer does not necessarily result in transfer failure. Using a model system comprising gold NPs and amphiphilic polymers, we demonstrate an unusual mechanism by which NPs can undergo phase transfer from the aqueous phase to the organic phase via a single‐aggregation‐single pathway. Our discovery challenges the conventional idea that aggregation inhibits NP transfer and provides an unexpected pathway for transferring larger‐sized NPs (>20 nm). The charged amphiphilic polymers effectively act as chaperons for the NP transfer and offer a unique way to manipulate the dispersion and distribution of NPs in two immiscible liquids. Moreover, by intentionally jamming the NP‐polymer assembly at the liquid/liquid interface, the transfer process can be inhibited.
Dual‐emissive Iridium(III) Complexes as Phosphorescent Probes with Orthogonal Responses to Analyte Binding and Oxygen Quenching
Authors: Zhu Rongji , Dai Peiling , Yang Jun , Zhou Jie , Zhang Jin , Zhang Kenneth Yin , Li Yonghua , Liu Shujuan , Lo Kenneth Kam‐Wing , Zhao Qiang
Published: July 2023

Phosphorescent probes often show sensitive response toward analytes at a specific wavelength. However, oxygen quenching usually occurs at the same wavelength and thus hinders the accurate detection of analytes. In this study, we have developed dual‐emissive iridium(III) complexes that exhibit phosphorescence responses to copper(II) ions at a wavelength distinct from that where oxygen quenching occurs. The complexes displayed colorimetric phosphorescence response in aqueous solutions under different copper(II) and oxygen conditions. In cellular imaging, variation in oxygen concentration over a large range from 5 % to 80 % can modulate the intensity and lifetime of green phosphorescence without affecting the response of red phosphorescence toward intracellular copper(II) ions.