bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural population dynamics of computing with synaptic modulations
Authors: Aitken Kyle , Mihalas Stefan
Published: February 2023

In addition to long-timescale rewiring, synapses in the brain are subject to significant modulation that occurs at faster timescales that endow the brain with additional means of processing information. Despite this, models of the brain like recurrent neural networks (RNNs) often have their weights frozen after training, relying on an internal state stored in neuronal activity to hold task-relevant information. In this work, we study the computational potential and resulting dynamics of a network that relies solely on synapse modulation during inference to process task-relevant information, the multi-plasticity network (MPN). Since the MPN has no recurrent connections, this allows us to study the computational capabilities and dynamical behavior contributed by synapses modulations alone. The generality of the MPN allows for our results to apply to synaptic modulation mechanisms ranging from short-term synaptic plasticity (STSP) to slower modulations such as spike-time dependent plasticity (STDP). We thoroughly examine the neural population dynamics of the MPN trained on integration-based tasks and compare it to known RNN dynamics, finding the two to have fundamentally different attractor structure. We find said differences in dynamics allow the MPN to outperform its RNN counterparts on several neuroscience-relevant tests. Training the MPN across a battery of neuroscience tasks, we find its computational capabilities in such settings is comparable to networks that compute with recurrent connections. Altogether, we believe this work demonstrates the computational possibilities of computing with synaptic modulations and highlights important motifs of these computations so that they can be identified in brain-like systems.
High-throughput sequencing approach for the identification of lncRNA biomarkers in hepatocellular carcinoma and revealing the effect of ZFAS1/miR-150-5p on hepatocellular carcinoma progression
Authors: Zhu Peng , Pei Yongyan , Yu Jian , Ding Wenbin , Yang Yun , Liu Fuchen , Liu Lei , Huang Jian , Yuan Shengxian , Wang Zongyan , Gu Fangming , Pan Zeya , Chen Jinzhong , Qiu Jinrong , Liu Huiying
Published: February 2023

Aims

To screen abnormal lncRNAs and diagnostic biomarkers in the progression of hepatocellular carcinoma through high-throughput sequencing and explore the underlying mechanisms of abnormal lncRNAs in the progression of hepatocellular carcinoma.

Methods

The transcriptome sequencing was used to analyze the RNA expression profile and identify differentially expressed RNAs. Hub lncRNAs were screened by combining (WGCNA, ceRNA regulatory network, PPI, GO and KEGG analyses, Kaplan-Meier curve analysis, Cox analysis, risk model construction and qPCR). Thereafter, the correlation between the expression of hub lncRNAs and tumor clinicopathological parameters was analyzed, and the hub lncRNAs were analyzed by GSEA. Finally, the effects of hub RNAs on the proliferation, migration and invasion of HepG2 cells were investigated in vitro.

Results

Compared with the control group, a total of 610 lncRNAs, 2,593 mRNAs and 26 miRNAs were screened in patients with hepatocellular carcinoma. Through miRNA target prediction and WGCNA, a ceRNA was constructed, comprising 324 nodes and 621 edges. Enrichment analysis showed that mRNAs in ceRNA were involved mainly in cancer development progression. Then, the ZFAS1/miR-150-5p interaction pair was screened out by Kaplan Meier curve analysis, Cox analysis and qPCR analysis. Its expression was related to tumor stage, TNM stage and patient age. ROC curve analysis showed that it has a good predictive value for the risk of hepatocellular carcinoma. GSEA showed that ZFAS1 was also enriched in the regulation of immune response, cell differentiation and proliferation. Loss-of-function experiments revealed that ZFAS1 inhibition could remarkably suppress HepG2 cell proliferation, migration and invasion in vitro. Bioinformatic analysis and luciferase reporter assays revealed that ZFAS1 directly interacted with miR-150-5p. Rescue experiments showed that a miR-150-5p inhibitor reversed the cell proliferation, migration and invasion functions of ZFAS1 knockdown in vitro.

Conclusion

ZFAS1 is associated with the malignant status and prognosis of patients with hepatocellular carcinoma, and the ZFAS1/miR-150-5p axis is involved in hepatocellular carcinoma progression.
Postoperative Analgesia in Ultrasound-Guided 3-in-1 Block versus Fascia Illiaca Compartment Block in Adult Patients Undergoing Lower Limb Orthopaedic Surgeries under General Anaesthesia: A Randomised Clinical Study
Authors: Keerthana S , Nagpal Vijay Kumar , Hariharan Uma , Kaur Mohandeep
Published: February 2023

Introduction: Three-in-one block and Fascia Illiaca Compartment Block (FICB) are two peripheral nerve block techniques that target the femoral nerve, obturator nerve and lateral femoral cutaneous nerve in a single injection. Both nerve blocks are used to provide anaesthesia and analgesia to the lower limb for various surgical procedures. The use of ultrasonography in peripheral nerve blocks helps to visualise the nerve, needle, and the distribution of the drug in real-time. It, thus, shortens the time of onset of sensory block, decreases performance time, and lowers the required drug doses, and finally increases chances of a favourable outcome from the nerve block. Aim: To compare the postoperative analgesic efficiency of ultrasound-guided 3-in-1 block with FICB in patients undergoing lower limb orthopaedic surgeries under General Anaesthesia (GA). Materials and Methods: A randomised clinical study was conducted at a tertiary care hospital. One hundred and fifty patients were randomly allocated to two groups, 3-in-1 block group or FICB. Both groups received the respective blocks after surgery before extubation. Postoperatively, Visual Analog Scale (VAS) scores were evaluated hourly for first 6 hours and 2 hourly thereafter until rescue analgesia was instituted. Time period from giving the block to giving rescue analgesia was noted as duration of analgesia. Injection diclofenac 1.5 mg/kg Intravenous (IV) was given when VAS value reached ≥4. Results: On analysis of 150 patients, divided into 3-in-1 block group (N=75) and FICB Group(N=75); mean age: 53.29±8.69 years; the VAS scores at 2 to 18 hours, 20 hours, and 22 hours after performing the blocks were significantly less in the 3-in-1 block group compared to FICB group. Also, the mean time (hours) for first rescue analgesia in FICB group (3.49±0.53) was earlier compared with 3-in-1 block group (7.35±0.51). Conclusion: A 3-in-1 block provides effective and prolonged postoperative analgesia in comparison to FICB.
Granular Cell Ameloblastoma: A Rare Case Report and Literature Review
Authors: Khan Samiha Jameel Ahmed , Gawande Madhuri , Hande Alka , Patil Swati , Sonone Archana
Published: February 2023

Ameloblastomas are rare, benign, aggressive neoplasms of odontogenic epithelial origin. Among the various types of ameloblastomas, granular cell ameloblastoma is rare and accounts for less than 5% of the total. Granular cells are epithelial in origin. The distinct histopathological characteristics of granular cells are associated with high lysosomal content in tumour cells cytoplasm. A 43-yearold female patient presented with a painful swelling on the left-side of the jaw. The diagnosis was based on clinical, radiological and histopathological examination. A complete surgical resection was done. Histopathology showed features of granular cell ameloblastoma. The operative procedure was uneventful. Granular cell ameloblastoma has a high tendency for recurrence. Around 33.3% recurrence is reported, according to various studies. This rate is much higher than other subtypes of ameloblastoma, which are more common. Hence, it is essential to provide appropriate surgical treatment on time to prevent tumour recurrence and metastasis.This case report aims to highlight the unique features of granular cell ameloblastoma, distinguishing it from other subtypes and discussing the pathogenesis and treatment modalities.
Synbiotic Yogurt Fortified with Bawang Dayak (Eleutherine palmifolia) Extract
Authors: Andriani R. D. , Sawitri M. E. , Widayanti V. T. , Manab A. , Rahayu P. P. , Fadilah R. N.
Published: February 2023

Aims: The purpose of this research was to study the quality of yogurt symbiotic fortified with Bawang Dayak (Eleutherine palmifolia) extract.

Study Design: This research used Completely Randomized Design (CRD) experimental method and consist of 4 treatments.

Place and Duration of Study: Sample: Animal Product Technology Laboratory Faculty of Animal Science Universitas Brawijaya, Food Quality and Safety Testing Laboratory Department of Agricultural Product Technology, Faculty of Agricultural Technology Universitas Brawijaya, between June 2022 – December 2022.

Methodology: The material used are skim milk, fresh milk, yogurt starter bacteria (Lactobacillus bulgaricus, Streptococcus thermophilus, Lactobacillus acidophillus), and bawang dayak extract. Bawang Dayak were extracted using Microwave-Asisted Extraction (MAE) with temperature 60-700C. This research which consist of 4 treatments and 3 replications with various concentration of Bawang Dayak extract of T0 (0%), T1 (1%), T2 (4%), and T3 (6%), respectively. The samples of synbiotic yogurt with fortification of Bawang Dayak extract were analyzed for their total lactic acid bacteria, antioxidant activity, viscosity and color analysis.

Results: Fortification of Bawang dayak extract in synbiotic yogurt results in highly significant different effects on the quality parameters of antioxidant and color (lightness, redness and yellowness) (P<0.01), but had no significant effect (P>0.05) on the total quality of lactic acid bacteria. Fortification of 6% Bawang dayak extract (T3) in yogurt produced the best quality in terms of antioxidant content and color (lightness, redness, and yellowness).

Conclusion: The best treatment of synbiotic yogurt was achieved in T3 with the 6% of Bawang Dayak extract.
Screening of Mung Bean Genotypes against Yellow Mosaic Virus (YMV) Resistance
Authors: Choudhary Anita , Choudhary Sushila , Singh Mahabeer , Yadav Vijay Laxmi , Moond Vishnu
Published: February 2023

Experiment was conducted to identify the resistant Mung bean varieties against MYMV in Kharif during 2017. Ten Indian mung bean genotypes obtained from AICRP on Arid legumes, RARI, Durgapura, Jaipur, were used in the screening experiment and the obtained results revealed that there was significant variation among the genotypes for resistance against MYMV. Based on the average MYMV score, only two genotypes (IPM 02-3 and IPM 0205-7) were found completely free from the disease and the plants had maximum chlorophyll content whereas IPM-409-4 and RMG 991 were found resistant and chlorophyll content was low as compared to the highly resistant genotypes. The rest of six genotypes observed moderately resistant, moderately susceptible, susceptible and highly susceptible to the disease.
Comparative Assessment of Farmer’s Brinjal Variety in Different Agro-Climatic Conditions
Authors: Choudhary Hardev , Dave Parthkumar P. , Parvez Noushad , Chodvadiya Mahesh B. , Ritaparna Prajana , Khuman Laishram Yelhounganba , Ipe Chriss , Sahu Leelaram
Published: February 2023

In order to evaluate the performance and suitability of the long brinjal variety ‘Niranjan Bhata’ developed by an innovative farmer of Chhattisgarh in different agro-climatic conditions of the country, the comparative field experiment conducted under Gandhinagar, Gujarat condition was accommodated in a randomized complete block design comprising five replications of four treatments, i.e. Niranjan Bhata, Pusa Shamla as National Check (NC) and two Local Check (LC) during June - March 2016. The plant height of Niranjan Bhata (115.50 cm) was recorded at par with LC-1 (118.33 cm). However, the maximum fruit length (45.80 cm) was recorded in Niranjan Bhata (45.80 cm). The significant highest fruit yield was produced by Niranjan Bhata (31.40 t/ha).

Farmer managed trials (FMTs) were also carried out in five states between 2017-18 and 2020-21 at 68 locations (loc.) during the Kharif season. The test variety ‘Niranjan Bhata’ reported superior performance in Chhattisgarh with the highest plant height (161.17 cm), fruit length (59.67 cm), and marketable fruit yield (9.81 kg/plant). The variety also outperformed with similar characters in Gujarat and Maharashtra states over checks. As per the growers' feedback, the variety was found to be high-yielding. The long fruits containing lesser seeds and soft pulp having good market preference too. Thus the evaluation of variety with the farmers’ participation was found most suitable approach which assured the varietal preference and its suitability for large-scale dissemination.
Water Requirements of Wheat Crops in a Small Watershed by Using CROPWAT
Authors: Ranjan Abhishek , Denis Derrick Mario , Sherring Arpan , Kumar Mukesh , Singh Vikram , Masih Shalini
Published: February 2023

A study was conducted to determine the water demand of wheat crops in the area around the Tonna Pumping Canal. It used 2017-2018 climate data to determine the need for wheat crops in water in CROPWAT. Reference crop evapotranspiration (ETo) was determined using the FAO Penman Monteith method. When considering wheat crops, four stages of crop growth were considered: early stage, development stage, mid-maturity, and late-maturity stages. Crops were planted in the 2017 rabi season and yields were determined for each.This study shows that baseline evapotranspiration (ETo) in the study area ranges from 1.48 to 3.98 mm/day. Crop evapotranspiration (ETc) and water demand for wheat crops ranged from 0.44 to 3.75 mm/day and 1.9 to 39.8 mm/day. The maximum water demand was 0.13 l/s/ha or 1.1 mm/day with 65% efficiency. The irrigation water demand was estimated at about 27.93 mm/day, and the actual water intake was 81,000.29 m3. The canal can therefore provide a convenient supply of the water needed to irrigate the area.
Assessment of Available Water and Crop Water Requirements of Major Crops in Nagarjuna Sagar Right Canal Command Area, Andhra Pradesh, India
Authors: Rao D. Sai Gangadhara , Krishna Ch. Murali , Kumar H. V. Hema , Devi B. Sarojini , Edukondalu L. , Rao V. Srinivasa
Published: February 2023

The mean water releases at head section of 11 years of Nagarjuna Sagar Jawahar right main Canal, Andhra Pradesh, India is found to be 128.13 TMC (3,627.71 MCM). The mean surface water availability was estimated as 2,229 MCM. For the efficient utilization of groundwater, the quality plays a major role in terms of selection of crop variety for sustainable agriculture. The ground water quantity of the command area available was estimated 1385 MCM and the mean annual conjunctive use of command area was 3,614 MCM (128 TMC).

The crop water requirement for paddy, cotton, chilies, millet and pulses were estimated in the command area by using CROPWAT model. The crop water requirement for paddy in NSRC command area of Guntur district for black soils was 848.2 mm. The irrigation water requirement was 638.9 mm and for red soils, crop water requirement for paddy and irrigation water requirements were 848.2 mm and 624.5 mm respectively. Similarly, computed for all the crops and overall crop water demand for both (Guntur and Prakasam) districts of NSRC command area for different soils and different crops per annum was 4,456 MCM without considering cattle and domestic water use. Based on the research, it was concluded that the available water is not sufficient and it is suggested to choose alternative crops for bringing entire area into cultivation.
Role of Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy in Evaluation of Different Types of Dementia
Authors: Esawy Abeer Salah Abd El Razek El , Younis Rasha Lottfy , Din ELSayed Aly Mohamed Tag EL , Dawoud Mahmoud Abd El Aziz
Published: February 2023

Aims: The aim of this work is to study the role of magnetic resonance imaging and magnetic resonance spectroscopy in evaluation of dementia patients.

Patients and Methods: This study conducted on fifty patients referred to radio diagnosis and medical imaging department from Neuropsychiatry department at Tanta University Hospital with clinical diagnosis of different types of dementia. 

Results: The grade of medial temporal lobe atrophy was higher in AD than in the other two types of dementia. Vascular lesions that fulfill these criteria were present in all patients diagnosed as VaD and their Fazekas score was 3, while patients diagnosed as AD and PDD didn’t have vascular lesions that fulfill NINDS-AIREN criteria and Fazekas scoring of these patients did not exceed 2. Decreased NAA/Cr ratio in the posterior cingulate gyrus was less valuable in diagnosing AD when compared with elevated mI/Cr. Decreased NAA/Cr ratio in the centrum semiovale, Decreased NAA/Cr ratio in the occipital lobe.

Conclusion: MRS is complementary to MRI revealing variable underlying metabolic abnormalities in different dementia subtypes even in cases with apparently normal conventional MRI series. Elevated mI/Cr ratio in the posterior cingulate gyrus is useful indicator when assessing Alzheimer’s dementia and also differentiating it from Vascular dementia and Parkinson’s disease dementia. Decrease in NAA/Cr ratio in the centrum semiovale is useful indicator when assessing suspected vascular dementia. Decrease in NAA/Cr ratio in the occipital lobe is useful indicator when assessing suspected Parkinson’s disease dementia.
A Comparative Model Analysis of Predictors of Community Pharmacists’ Collaborative Practices in Two Southwestern States in Nigeria
Authors: Oamen Theophilus Ehidiamen
Published: February 2023

Background: In community pharmacy practice, pharmacists are expected to engage in collaborative activities to deliver quality service to clients. However, due to the hybrid nature (social and commercial dimensions) of the practice, certain subjective behavioral norms-competitive and information-sharing behavior may have potential influence on the collaborative behaviors of community pharmacists

Objectives: Based on the theory of planned behavior framework, the study tests the influence of subjective norms-competitive behavior and information-sharing practices on the collaborative behavior of community pharmacists; and, investigated possible differences in the perception of respondents in two southwestern states in Nigeria

Methods: A cross-sectional quantitative study with randomly administered questionnaires to 421 community pharmacists from two purposively selected states- Lagos (230) and Ogun (191) in southwest Nigeria. A structural equation model was developed using Analysis of Moment Structures software (AMOS). Group differences were evaluated using the chi-square difference test.

Results: Competitive behavior and information-sharing behavior are substantial predictors of collaborative behaviors among community pharmacists (R2=0.97, p<0.001). Multigroup analysis revealed differences in perception between respondents in the densely populated and less densely populated settings. Model comparisons revealed insignificant group differences.

Conclusion: The study confirmed that information-sharing and competitive behavior have a positive and significant influence on collaborative behavior. The findings of the study imply that no link exists between the geographical placement of community pharmacists and differences in their practice behavior. Professional associations and regulatory bodies should provide training and engage in participatory workshops to strengthen the right collaborative attitudes among community pharmacists. The study provides a theoretical framework for further studies in inter- and intra-professional relations among healthcare professionals.
Experimental Study of Self-Compacting Concrete Using Plantain Leaf Ash and Polycarboxylate Ether Solution as Superplasticizer
Authors: Tochukwu Mmeka Paschal , Emeka Ugwu Stephen , Chisomnazu Iwenofu Alvin
Published: February 2023

Concrete is a binding material, made up of constituent of cement, fine aggregate, coarse aggregate and water. Self-Compacting Concrete is an innovative concrete that does not require vibration for placing and compaction. It is able to flow under its own weight, completely filling formwork and achieving full compaction, even in the presence of congested reinforcement. The study also intended to quantify the amount of plantain leaf ash to be added to the concrete according to the value of concrete properties measured. For such purpose, the fresh concrete must possess intense fluidity and great cohesiveness. Plantain leaf ash is waste and is causing threat to environment in terms of odour and to reduce this problem of this material the project has been undertaken so that it can be used for construction purpose. The following points were attempted for the resdearch;
  i.   To replace cement by different percentage of Plantain leaf ash,
  ii.  To prepare concrete by replacing the cement by Plantain leaf ash,
  iii. To compare the fresh properties of self-compacting concrete containing varying amounts of plantain leaf ash with that containing commercially available superplasticizer,
  iv. To study the compressive strength of normal conventional concrete and self-compacting concrete.
Analysis of Financial Statement Preparation, Fiscal Reconciliation and Human Resources Competency on Corporate Income Tax of Sriwijaya Argo Sakti Company, Indonesia
Authors: Yunita Hesti
Published: February 2023

Aims: This study aims to find out, analyze, and how the competence of human resources in the internal PT SAS and fiscal correction and analyze whether the competence of internal human resources is an obstacle or supporting factor in preparing financial statements.

Study Design:  The research design used in this study is a qualitative descriptive research design using the post-positivism paradigm with the triangulation method, which is an experimental approach using various methods, data sources, researchers, and theories.

Place and Duration of Study: The researcher set an analysis unit on the Corporate Income Tax (PPh) Fiscal Correction and reviewed PT SAS's 2020 financial statements with Human Resources (HR) as an influential factor. Sampling determination in this study used a purposive sampling technique.

Methodology: The sampling determination in this study used purposive sampling techniques with the criteria of PT SAS Tax Managers, Tax Consultants, Accounting Staff, and Tax Staff. The data collection used in this study can be grouped into two categories, namely interactive and non-interactive methods.

Results: Based on the study's results, a fiscal correction in corporate income tax was caused by HR errors that did not record accounts receivable. Then, there is the fiscal correction. From the aspect of knowledge (knowledge), attitude (attitude) and aspects of skills (skills), there are still problems that still need to be solved.

Conclusion: The company must be more thorough in making corrections to the costs that the company has incurred according to the rules. Companies should more often provide education and training in the field of accounting and taxation to employees. The company also advises the directorate general of taxes to review related CSR Costs.
The heritage of disorganised attachment
Authors: Appel Stephen , Healy Catherine
Published: February 2023

Clients who characteristically relate in a disorganised way present particular clinical difficulties. A better understanding of what might be going on for the client is helpful to the therapist in the face of the client's erratic responses. To that end we offer this article which provides a description of disorganised attachment and reviews a selection of recent studies in several fields in order to better comprehend the heritage of disorganised/disoriented attachment behaviour, its precursors and outcomes. We include a heuristic framework of the emotional socialization of attachment. The article ends with some thoughts on psychotherapy with disorganised clients attachment and proposes a story-reclaiming framework.
Psychotherapy as fiction
Authors: Culbertson Philip
Published: February 2023

This past year, two major psychotherapists each published a novel. Struck by this coincidence, I decided to explore the historical relationship between novels and psychotherapy, focusing on psychotherapy by novels, psychotherapy in novels, and psychotherapists as novelists. Particular attention is given to Slavoj Žižek's theories of the detective story as an analogue for psychoanalysis.
Multinational Analysis of Estimated Health Care Costs Related to Extended-Interval Fixed Dosing of Checkpoint Inhibitors
Authors: Goldstein Daniel A. , Ginsberg Gary M. , Hofnung-Gabbay Dorit , De Abreu Lourenco Richard , Loong Herbert H. , Goh Boon Cher , Chan Kelvin K. W. , Di Maio Massimo , Perrone Francesco , Hall Peter S. , Zer Alona , Rosenbaum Eli
Published: February 2023

Importance

New dosing options for immune checkpoint inhibitors have recently been approved by the US Food and Drug Administration (FDA), including fixed dosing with extended intervals. Although the dose intensity appears the same, there is expected to be some waste with extended-interval dosing, as some drug remains in the bloodstream once a decision to stop treatment is made. The economic impact of extended-interval fixed dosing is unknown compared with standard-interval fixed dosing.

Objective

To analyze the potential health care costs of using extended-interval fixed dosing instead of standard-interval fixed dosing.

Design, Setting, and Participants

This economic evaluation used a pharmacoeconomic model to simulate 2 cohorts of patients with platinum-resistant metastatic urothelial cancer receiving pembrolizumab as second-line therapy at different dosing intervals using 2020 pricing data. Data were analyzed from 2020 to 2022.

Exposures

The simulated patients received FDA-approved regimens of either 200 mg every 3 weeks or 400 mg every 6 weeks.

Main Outcomes and Measures

The progression-free survival curve from the KEYNOTE-045 trial was used to estimate treatment duration. Drug, imaging, and administration costs were included in analyses. Sensitivity analyses were performed to assess how different imaging frequencies would affect the model results. The potential overall costs of using the 2 different dosing strategies were assessed. The base case was set in the US, while sensitivity analyses were set in several other countries.

Results

In the base case analysis, dosing every 6 weeks instead of every 3 weeks resulted in an estimated 8.9% increase in pembrolizumab costs for the health care payer. Accounting for a decrease in infusion costs would result in an estimated net additional cost of $7483 per patient in the US (7.9% cost increase). In the US, this would amount to an increase of approximately $28 million annually for health care payers. Similar percentages in cost estimate increases were found for health care payers around the world, such as in Israel, where the net additional cost would be $5491 per patient.

Conclusions and Relevance

This economic evaluation assessed and quantified the potential increased costs related to extended-interval fixed dosing of pembrolizumab. The model method could be applied to other diseases and other drugs for which there has been a movement toward extended-interval dosing. Results may differ in other diseases owing to differing disease courses and patient profiles.
Detection of the Omicron BA.1 Variant of SARS-CoV-2 in Wastewater From a Las Vegas Tourist Area
Authors: Vo Van , Tillett Richard L. , Papp Katerina , Chang Ching-Lan , Harrington Anthony , Moshi Michael , Oh Edwin C. , Gerrity Daniel
Published: February 2023

Importance

Interpretation of wastewater surveillance data is potentially confounded in communities with mobile populations, so it is important to account for this issue when conducting wastewater-based epidemiology (WBE).

Objectives

To leverage spatial and temporal differences in wastewater whole-genome sequencing (WGS) data to quantify relative SARS-CoV-2 contributions from visitors to southern Nevada.

Design, Setting, and Participants

This cross-sectional wastewater surveillance study was performed during the COVID-19 pandemic (March 2020 to February 2022) and included weekly influent wastewater samples that were analyzed by reverse transcription–quantitative polymerase chain reaction to quantify SARS-CoV-2 RNA and WGS for identification of variants of concern. This study was conducted in the Las Vegas, Nevada, metropolitan area, which is a semi-urban area with approximately 2.3 million residents and nearly 1 million weekly visitors. Samples were collected from 7 wastewater treatment plant (WWTP) locations that collectively serve the vast majority of southern Nevada (excluding the small number of septic systems) and 1 manhole serving the southern portion of the Las Vegas Strip. With Las Vegas tourism returning to prepandemic levels in 2021, it was hypothesized that visitors were contributing a disproportionate fraction of SARS-CoV-2 RNA to the largest WWTP in southern Nevada, potentially confounding efforts to estimate COVID-19 incidence in the local community through WBE.

Main Outcomes and Measures

Relative SARS-CoV-2 load and variants from visitors vs the local population.

Results

The Omicron BA.1 VOC was detected in the Las Vegas Strip manhole approximately 1 week before its detection at the WWTP locations (December 13, 2021) and by clinical testing (December 14, 2021). On December 13, Omicron-specific mutations represented a mean (SD) of 48.0% (4.2%) of all genomes from the Las Vegas Strip manhole and 4.1% (1.4%) of all genomes at facilities 2 and 3; by December 20, Omicron-specific mutations represented means (SD) of 82.0% (3.0%) of all genomes at the Las Vegas Strip manhole and 48.0% (2.8%) of all genomes at facilities 2 and 3, respectively. During this time, it was estimated that visitors contributed more than 60% of the SARS-CoV-2 load to the sewershed serving the Las Vegas Strip and that Omicron prevalence among visitors was 40% to 60% on December 13 and 80% to 100% on December 20th.

Conclusions and Relevance

Wastewater surveillance is a valuable complement to clinical tools and can provide time-sensitive data for decision-makers and policy makers. This study represents a novel approach for quantifying the confounding effects of mobile populations on wastewater surveillance data, thereby allowing for modification of an existing WBE framework for estimating COVID-19 incidence in southern Nevada.
ERBB2-Low (Also Known as HER2-Low) Breast Cancer
Authors: Idossa Dame , Borrero Maria , Blaes Anne
Published: February 2023

This JAMA Oncology Patient Page discusses classification of breast cancer and ERBB2 status.
Estimates and Projections of the Global Economic Cost of 29 Cancers in 204 Countries and Territories From 2020 to 2050
Authors: Chen Simiao , Cao Zhong , Prettner Klaus , Kuhn Michael , Yang Juntao , Jiao Lirui , Wang Zhuoran , Li Weimin , Geldsetzer Pascal , Bärnighausen Till , Bloom David E. , Wang Chen
Published: February 2023

Importance

Cancers are a leading cause of mortality, accounting for nearly 10 million annual deaths worldwide, or 1 in 6 deaths. Cancers also negatively affect countries’ economic growth. However, the global economic cost of cancers and its worldwide distribution have yet to be studied.

Objective

To estimate and project the economic cost of 29 cancers in 204 countries and territories.

Design, Setting, and Participants

A decision analytical model that incorporates economic feedback in assessing health outcomes associated with the labor force and investment. A macroeconomic model was used to account for (1) the association of cancer-related mortality and morbidity with labor supply; (2) age-sex-specific differences in education, experience, and labor market participation of those who are affected by cancers; and (3) the diversion of cancer treatment expenses from savings and investments. Data were collected on April 25, 2022.

Main Outcomes and Measures

Economic cost of 29 cancers across countries and territories. Costs are presented in international dollars at constant 2017 prices.

Results

The estimated global economic cost of cancers from 2020 to 2050 is $25.2 trillion in international dollars (at constant 2017 prices), equivalent to an annual tax of 0.55% on global gross domestic product. The 5 cancers with the highest economic costs are tracheal, bronchus, and lung cancer (15.4%); colon and rectum cancer (10.9%); breast cancer (7.7%); liver cancer (6.5%); and leukemia (6.3%). China and the US face the largest economic costs of cancers in absolute terms, accounting for 24.1% and 20.8% of the total global burden, respectively. Although 75.1% of cancer deaths occur in low- and middle-income countries, their share of the economic cost of cancers is lower at 49.5%. The relative contribution of treatment costs to the total economic cost of cancers is greater in high-income countries than in low-income countries.

Conclusions and Relevance

In this decision analytical modeling study, the macroeconomic cost of cancers was found to be substantial and distributed heterogeneously across cancer types, countries, and world regions. The findings suggest that global efforts to curb the ongoing burden of cancers are warranted.
Evaluation and Follow-up of Myopia Prevalence Among School-Aged Children Subsequent to the COVID-19 Home Confinement in Feicheng, China
Authors: Wang Jiaxing , Han Yujie , Musch David C. , Li Ying , Wei Nan , Qi Xiaoli , Ding Gang , Li Xue , Li Jing , Song Linlin , Zhang Ying , Ning Yuxian , Zeng Xiaoyu , Li Yaoling , Sun Ling , Hua Ning , Li Shuo , Jardines Sandra , Qian Xuehan
Published: February 2023

Importance

Progression of myopia in a school-aged population due to home confinement (January to May 2021) during the COVID-19 pandemic has been previously reported. A key remaining question was whether the myopia spike in children aged 6 to 8 years persisted.

Objective

To investigate the changes in refractive status and prevalence of myopia in school-aged children 1 year after home confinement ended in China.

Design, Setting, and Participants

This cross-sectional study with a cohort substudy prospectively evaluated data from school-based photoscreening in Feicheng, China. Children aged 6 to 13 years participated in 8 screenings from 2015 to 2021.

Exposures

Noncycloplegic photorefraction was conducted using the Spot Vision photoscreener.

Main Outcomes and Measures

The main outcomes were the differences in spherical equivalent refraction (SER) and prevalence of myopia between 2020 (during home confinement) and 2021 (after home confinement). The SER was recorded for each child, and the prevalence of myopia was calculated annually for each age group.

Results

A total of 325 443 children participated in the study (51.4% boys, 48.6% girls; age range, 6 to 13 years). Compared with 2020, the mean SER of children in 2021 increased significantly for those aged 6 (0.42 diopters [D]), 7 (0.41 D), and 8 (0.33 D) years. The prevalence of myopia in 2021 was similar to in 2019 for each age group (aged 6 years: 7.9% vs 5.7%; aged 7 years: 13.9% vs 13.6%; aged 8 years: 29.5% vs 26.2%). Both the prevalence of myopia and mean SER for these children returned to their prepandemic levels.

Conclusions and Relevance

Compared with 2020, the prevalence of myopia among children aged 6 to 8 years in the 2021 screenings decreased, and the mean SER returned to prepandemic level. The refractive development in children aged 6 to 8 years may be most susceptible to environmental changes. These findings support the premise that age 6 to 8 years is a critical period for myopia development and suggest a need to focus preventive interventions for myopia control on children in this age range.
Drug-Induced Sleep Endoscopy Differences by Age in Surgically Naive Children With Sleep-Disordered Breathing
Authors: Herzig Maya X. , Hildebrand Andrea D. , Nguyen Thuan , Lam Derek J.
Published: February 2023

Importance

Drug-induced sleep endoscopy (DISE) is increasingly used to guide treatment decisions in children with sleep-disordered breathing (SDB). Previous reports of DISE findings in children have typically included a broad age range, but it is unclear how these patterns of obstruction vary with age.

Objective

To compare patterns of airway obstruction observed during DISE in 3 age groups of surgically naive children with SDB.

Design, Setting, and Participants

This cross-sectional analysis of a prospective cohort of surgically naive nonsyndromic children with SDB or obstructive sleep apnea [OSA] at risk for residual disease after adenotonsillectomy (defined as having at least 1 of these criteria: severe OSA, older than 7 years, obesity, or Black race) who were recruited between May 1, 2015, and February 28, 2020, was conducted at a tertiary children’s hospital. Data analysis was conducted from September 2021 to February 2022.

Exposures

DISE.

Main Outcomes and Measures

DISE findings were rated at 6 anatomic sites using the Sleep Endoscopy Rating Scale (SERS). The association between age and severity of obstruction at each anatomic site and overall were compared using correlation (Kendall τ) and ordinal logistic regression analysis.

Results

Data from 288 children (144 girls [50%]; 20 American Indian/Alaska Native [7%], 4 Asian [1%], 19 Black [7%], 93 Hispanic [33%], 2 Middle Eastern [1%], 6 Native Hawaiian/Pacific Islander [2%], and 203 White [70%] individuals; median [IQR] age, 9.2 [7.0-11.7] years) were stratified by participant age into preschool (age 2-5 years; 27 [9%]), younger school-aged (age 5-10 years; 146 [51%]), and older school-aged (age 10-18 years; 115 [40%]). Among these subgroups, the prevalence of multilevel obstruction was 59%, 51%, and 30%, respectively. Increasing age was inversely correlated with obstruction of the nasal airway (τb, −0.19; 95% CI, −0.29 to −0.09), nasopharynx (τb, −0.20; 95% CI, −0.31 to −0.10), velopharynx (τb, −0.16; 95% CI, −0.26 to −0.06), and overall obstruction (SERS total score: τb, −0.24; 95% CI, −0.33 to −0.14). An adjusted analysis demonstrated an inverse association between age and nasopharyngeal obstruction (odds ratio [OR], 0.84; 95% CI, 0.76 to 0.92), SERS total score (OR, 0.83; 95% CI, 0.76 to 0.90), and the number of sites of complete obstruction (OR, 0.87; 95% CI, 0.87 to 0.95).

Conclusions and Relevance

This cross-sectional analysis of data from a prospective cohort study of surgically naive children with SDB found that preschool-aged children had more frequent multilevel obstruction, more severe overall obstruction, and nasopharyngeal obstruction compared with older children. Understanding the most common sites of obstruction and expected changes with age could inform personalized treatment for children with SDB.
Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling
Authors: Teleanu Maria‐Veronica , Fuss Carmina T. , Paramasivam Nagarajan , Pirmann Sebastian , Mock Andreas , Terkamp Christoph , Kircher Stefan , Landwehr Laura‐Sophie , Lenschow Christina , Schlegel Nicolas , Stenzinger Albrecht , Jahn Arne , Fassnacht Martin , Glimm Hanno , Hübschmann Daniel , Fröhling Stefan , Kroiss Matthias
Published: February 2023

Parathyroid carcinoma (PC) is an ultra‐rare malignancy with a high risk of recurrence after surgery. Tumour‐directed systemic treatments for PC are not established. We used whole‐genome and RNA sequencing in four patients with advanced PC to identify molecular alterations that could guide clinical management. In two cases, the genomic and transcriptomic profiles provided targets for experimental therapies that resulted in biochemical response and prolonged disease stabilization: (a) immune checkpoint inhibition with pembrolizumab based on high tumour mutational burden and a single‐base substitution signature associated with APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide‐like) overactivation; (b) multi‐receptor tyrosine kinase inhibition with lenvatinib due to overexpression of FGFR1 (Fibroblast Growth Factor Receptor 1) and RET (Ret Proto‐Oncogene) and, (c) later in the course of the disease, PARP (Poly(ADP‐Ribose) Polymerase) inhibition with olaparib prompted by signs of defective homologous recombination DNA repair. In addition, our data provided new insights into the molecular landscape of PC with respect to the genome‐wide footprints of specific mutational processes and pathogenic germline alterations. These data underscore the potential of comprehensive molecular analyses to improve care for patients with ultra‐rare cancers based on insight into disease biology.
Pressure Engineering Toward Harvesting the Bright Deep‐Blue‐Light Emission in Y‐based Metal‐Organic Frameworks
Authors: Wang Yixuan , Liu Chuang , Yong Xue , Yang Xinyi , Yu Jingkun , Lu Siyu , Bai Fuquan , Wang Shiping , Wang Kai , Liu Zhaodong , Feng Bingtao , Hou Xuyuan , Liu Hao , Chen Banglin , Fang Qianrong , Zou Bo
Published: February 2023

The emergence of metal‐organic frameworks (MOFs) provides a new platform of low‐cost and color‐saturated blue light‐emitting diodes ideal for display and solid‐state lighting applications. However, numerous established MOFs still exhibit weak deep‐blue‐light emission (<450 nm) owing to low energy/charge transfer efficiency. Here a pressure‐treated strategy to greatly enhance photoluminescence performance of deep‐blue light‐emitting Y(BTC)(H2O)6 (H3BTC: benzene‐1,3,5‐tricarboxylic acid) is reported. Pressure‐treated Y(BTC)(H2O)6 exhibits a bright emission at 409 nm with a photoluminescence quantum yield from the initial 2.8% increasing to 75.0%. The hydrogen bonding cooperativity effect increases hydrogen bond binding energy after pressure treatment and thus the planarization structure is locked. The increased electronic transition diversity and oscillator strength originating from the planarization structure are highly responsible for boosting metal‐to‐ligand charge transfer. The findings in this study provide significant insights into the underlying mechanism of the structure‐property relationship in Y(BTC)(H2O)6 and offer a promising strategy to harvest deep‐blue‐emitting MOFs materials.
Controlled Interfacial Polymer Self‐Assembly Coordinates Ultrahigh Drug Loading and Zero‐Order Release in Particles Prepared under Continuous Flow
Authors: Zhang Pei , Liu Yingxin , Feng Guobing , Li Cong , Zhou Jun , Du Chunyang , Bai Yuancheng , Hu Shuai , Huang Tianhe , Wang Guan , Quan Peng , Hirvonen Jouni , Fan Jin , Santos Hélder A. , Liu Dongfei
Published: February 2023

Microparticles are successfully engineered through controlled interfacial self‐assembly of polymers to harmonize ultrahigh drug loading with zero‐order release of protein payloads. To address their poor miscibility with carrier materials, protein molecules are transformed into nanoparticles, whose surfaces are covered with polymer molecules. This polymer layer hinders the transfer of cargo nanoparticles from oil to water, achieving superior encapsulation efficiency (up to 99.9%). To control payload release, the polymer density at the oil–water interface is enhanced, forming a compact shell for microparticles. The resultant microparticles can harvest up to 49.9% mass fraction of proteins with zero‐order release kinetics in vivo, enabling an efficient glycemic control in type 1 diabetes. Moreover, the precise control of engineering process offered through continuous flow results in high batch‐to‐batch reproducibility and, ultimately, excellent scale‐up feasibility.
Analytical Physical Model for Electrolyte Gated Organic Field Effect Transistors in the Helmholtz Approximation
Authors: Huetter Larissa , Kyndiah Adrica , Gomila Gabriel
Published: February 2023

The analytical physical modeling of undoped electrolyte gated organic field effect transistors (EGOFETs) in the Helmholtz approximation is presented. A compact analytical model for the current–voltage (I–V) characteristics, which includes the effects of the access series resistance, has been derived and validated by means of 2D finite element numerical calculations. The model describes all operating regimes continuously (subthreshold, linear, and saturation regimes), covers channel lengths down to a few micrometres and only includes physical device parameters. From the model, analytical expressions have been proposed for all the phenomenological parameters (e.g., capacitance, threshold voltage, sub‐threshold slope voltage, and sub‐threshold capacitance) appearing in the commonly used ideal FET model. The derived analytical physical model provides a simple and quantitative way to analyze the electrical characteristics of EGOFETs and EGOFET biosensors beyond the use of the oversimplified and phenomenological ideal FET model.
H3K4 Methylation Promotes Expression of Mitochondrial Dynamics Regulators to Ensure Oocyte Quality in Mice
Authors: Mei Ning‐hua , Guo Shi‐meng , Zhou Qi , Zhang Yi‐ran , Liu Xiao‐zhao , Yin Ying , He Ximiao , Yang Jing , Yin Tai‐lang , Zhou Li‐quan
Published: February 2023

Significantly decreased H3K4 methylation in oocytes from aged mice indicates the important roles of H3K4 methylation in female reproduction. However, how H3K4 methylation regulates oocyte development remains largely unexplored. In this study, it is demonstrated that oocyte‐specific expression of dominant negative mutant H3.3‐K4M led to a decrease of the level of H3K4 methylation in mouse oocytes, resulting in reduced transcriptional activity and increased DNA methylation in oocytes, disturbed oocyte developmental potency, and fertility of female mice. The impaired expression of genes regulating mitochondrial functions in H3.3‐K4M oocytes, accompanied by mitochondrial abnormalities, is further noticed. Moreover, early embryos from H3.3‐K4M oocytes show developmental arrest and reduced zygotic genome activation. Collectively, these results show that H3K4 methylation in oocytes is critical to orchestrating gene expression profile, driving the oocyte developmental program, and ensuring oocyte quality. This study also improves understanding of how histone modifications regulate organelle dynamics in oocytes.
MIR497HG‐Derived miR‐195 and miR‐497 Mediate Tamoxifen Resistance via PI3K/AKT Signaling in Breast Cancer
Authors: Tian Yao , Chen Zhao‐Hui , Wu Peng , Zhang Di , Ma Yue , Liu Xiao‐Feng , Wang Xin , Ding Dan , Cao Xu‐Chen , Yu Yue
Published: February 2023

Tamoxifen is commonly used for the treatment of patients with estrogen receptor‐positive (ER+) breast cancer, but the acquired resistance to tamoxifen presents a critical challenge of breast cancer therapeutics. Recently, long noncoding RNA MIR497HG and its embedded miR‐497 and miR‐195 are proved to play significant roles in many types of human cancers, but their roles in tamoxifen‐resistant breast cancer remain unknown. The results indicate that MIR497HG deficiency induces breast cancer progression and tamoxifen resistance by inducing downregulation of miR‐497/195. miR‐497/195 coordinately represses five positive PI3K‐AKT regulators (MAP2K1, AKT3, BCL2, RAF1, and CCND1), resulting in inhibition of PI3K‐AKT signaling, and PI3K‐AKT inhibition in tamoxifen‐resistant cells restored tamoxifen responsiveness. Furthermore, ER α binds the MIR497HG promoter to activate its transcription in an estrogen‐dependent manner. ZEB1 interacts with HDAC1/2 and DNMT3B at the MIR497HG promoter, resulting in promoter hypermethylation and histone deacetylation. The findings reveal that ZEB1‐induced MIR497HG depletion contributes to breast cancer progression and tamoxifen resistance through PI3K‐AKT signaling. MIR497HG can be used as a biomarker for predicting tamoxifen sensitivity in patients with ER+ breast cancer.