bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating Frailty Assessment to Enhance Care in Cancer Patients with Borderline Eastern Cooperative Oncology Group Performance Status
Authors: Hsu Chih-Chung , Hung Yu-Shin , Yu Shao-Ming , Hsueh Shun-Wen , Chou Wen-Chi
Published: January 2024

Background

The (ECOG) performance status (PS) is commonly used to evaluate the functional ability of patients undergoing antitumor therapy. An ECOG PS of 2, indicating patients capable of self-care but restricted strenuous activity, can complicate treatment decisions owing to concerns regarding treatment-related toxicity. We investigated whether frailty assessment could help discriminate treatment tolerance and survival outcomes in patients with an ECOG PS of 2.

Methods

We prospectively included 45 consecutive patients, aged ≥65 years, with an ECOG PS of 2, and newly diagnosed solid cancer scheduled for chemotherapy. Frailty was assessed using an eight-indicator geriatric assessment. The primary outcome was overall survival (OS) based on frailty status; secondary outcomes included treatment tolerance and toxicity.

Results

The median patient age was 73 years (range 65-94), and 71% had stage IV disease. Predominant frailty-related deficits were functional decline (96%), malnutrition (78%), and polypharmacy (51%). The median OS was 12.6 months (95% confidence interval [CI]: 6.8-18.4). Patients with 4-6 deficits had significantly lower OS than those with 1-3 deficits (9.9 months vs. 20.0 months, adjusted hazard ratio 2.51, 95% CI: 1.16-5.44, P = .020). Frailty significantly correlated with reduced 12-week chemotherapy competence (52% vs. 85%, adjusted odds ratio [OR] .14, 95% CI: .03-.70, P = .016) and enhanced risk of unexpected hospitalization (60% vs. 20%, adjusted OR 6.80, 95% CI: 1.64-28.1, P = .008).

Conclusion

Our findings highlight the multifaceted nature of patients with an ECOG PS of 2 and emphasize the importance of frailty assessment for treatment outcomes.
LQG/LTR based robust youla parameterized adaptive vibration control for the supporting platform of rotating liquid mirror
Authors: Ding Haichun , Li Feng , Qian Fanfan , Xu Tingyue , Liu Tianqi , Wu Zhizheng , Sivanandam Suresh , Iqbal Azhar
Published: January 2024

In mechatronic systems, the vibrations which commonly consist of band-limited random signals mixed with large multiple narrow-band deterministic signals may negatively impact the system performance. For example, due to the incomplete matching of the mechanism and the rotation of the motor, random and deterministic vibration disturbance may occur in the supporting platform of the rotating liquid mirror. In this paper, a robust Youla ( Q) parameterized adaptive regulation approach has been proposed to minimize such kind of vibration signals for the rotating platform system with model uncertainties. Firstly, the inner-loop robust controller with linear quadratic Gaussian with loop transfer recovery ( LQG/LTR) is optimally designed by choosing the suitable weighting functions to achieve the trade-off between robust stability and control performance to deal with random vibration signals. Then the Youla parameter is augmented to construct a set of Q-parameterized stabilizing controllers, and the robust stability of the system is analyzed through dual-Youla parameterization of the uncertain model. The recursive least squares (RLS) adaptive algorithm is developed to tune the Q parameter online to construct a desired adaptive controller for further residual vibration elimination. An experimental evaluation of the controller in reducing the vibration of the supporting platform of a rotating liquid mirror has been carried out, and the results illustrate that the proposed adaptive robust vibration regulation approach can effectively suppress the band-limited random and narrow-band deterministic vibration signals.
Unraveling the Digital Threat: Exploring the Impact of Online Harassment on South Korean Journalists’ Professional Roles
Authors: Yeon Lee Na , Park Ahran
Published: January 2024

This research examines whether and to what extent journalists are harassed online and the effects of online harassment on their professional roles. The study classifies online harassment against journalists into five types: insults, threats, privacy intrusion, sexual assault, and cyber-hacking. The findings reveal a positive correlation between online harassment and various adverse outcomes for journalists, including increased self-censorship, reduced public engagement, and heightened skepticism toward journalism. With regard to a specific type of online harassment, journalists’ gender plays a role as a moderator: The relationship between insults and self-censorship, disengagement with the public, and skepticism toward journalism was found to be stronger for women journalists than men journalists.
A relative comparison of HCCI, PCCI, and RCCI combustion strategies: an alternative fuels perspective
Authors: Gupta Saurabh K , Krishnasamy Anand
Published: January 2024

Low temperature combustion (LTC) strategies have the potential for simultaneous reduction in oxides of nitrogen (NOx) and soot emissions while achieving higher thermal efficiency. Commercial widespread implementation of LTC strategies demands addressing several challenges, including narrow operating load range, lack of ignition timing control, and reducing high unburned hydrocarbon (HC) and carbon monoxide (CO) emissions. These challenges could be because the conventional engine design and fuels cannot adapt well to LTC modes. Thus, replacing conventional diesel fuel with suitable alternative fuels for LTC strategies is essential. In the present work, three LTC strategies, Homogenous Charge Compression Ignition (HCCI), Premixed Charge Compression Ignition (PCCI), and Reactivity Controlled Compression Ignition (RCCI), are compared with conventional diesel combustion in a production, light-duty diesel engine from an alternative fuel perspective to come up with a befitting strategy and fuel to achieve wider operating range and lower emissions. The fuel selection strategy based on the fundamental fuel property requirements of the three LTC strategies has been discussed in detail. The baseline reference data is fixed by comparing three LTC strategies with conventional diesel combustion using diesel and gasoline as reference fuel at 40% load, the maximum common achievable load among the three LTC strategies. This is followed by an investigation of the effect of alternative fuels across three LTC strategies to address the shortcomings of the LTC strategies. The results show that the engine operating load range could be extended, and HC and CO emissions are reduced significantly with alternative fuels in the three LTC strategies.
Sub-Saharan women in engineering higher education: A literature-informed research tool
Authors: Hailu Meseret F. , Parra Gaete Ivet
Published: January 2024

We present a review of higher education and education policy literature to understand better higher education institutions (HEIs) that serve sub-Saharan women in engineering. Our sub-Saharan women in engineering (SSAWE) literature-informed conceptual tool consists of five components to facilitate scholarly discussion about equity in higher education systems and facilitate interregional comparisons. The five components to study the educational experiences of women in engineering in this region include (1) a sociopolitical and historical national context for higher education policy, (2) critical discourse analysis of gender-based affirmative action policies, (3) enrollment and graduation data for female engineering students, (4) a longitudinal assessment of the employability of the engineering major, and (5) a qualitative campus climate survey of each country's flagship university. Our article introduces a conceptual investigation of the social, historical, and employment trends contextualizing engineering higher education in this region of Africa. We draw from existing literature about conceptual models predominantly used in higher education efforts toward undergraduate student success. When describing each SSAWE component, we include empirical and theoretical work that substantiates the need for each component and the benefits of the proposed methodology. More broadly speaking, this paper discusses how research employing the SSAWE framework could benefit key stakeholders who engage in policymaking. We suggest that sub-Saharan African universities should prioritize a regional comparative approach when designing support programs for underrepresented students in engineering. SSAWE will also generate more South–South comparisons that advance culturally situated analyses, contributing to higher education institutions’ advancementand the minoritized populations they serve.
Neuropsychiatric Behavioral Assessments in Mice After Acute and Long-Term Treatments of Low-Intensity Pulsed Ultrasound
Authors: Li Ye , Wu Yiqing , Luo Qi , Ye Xuanjie , Chen Jie , Su Yuanlin , Zhao Ke , Li Xinmin , Lin Jing , Tong Zhiqian , Wang Qi , Xu Dongwu
Published: January 2024

Introduction: To evaluate whether both acute and chronic low-intensity pulsed ultrasound (LIPUS) affect brain functions of healthy male and female mice. Methods: Ultrasound (frequency: 1.5 MHz; pulse: 1.0 kHz; spatial average temporal average (SATA) intensity: 25 mW/cm2; and pulse duty cycle: 20%) was applied at mouse head in acute test for 20 minutes, and in chronic experiment for consecutive 10 days, respectively. Behaviors were then evaluated. Results: Both acute and chronic LIPUS at 25 mW/cm2 exposure did not affect the abilities of movements, mating, social interaction, and anxiety-like behaviors in the male and female mice. However, physical restraint caused struggle-like behaviors and short-time memory deficits in chronic LIPUS groups in the male mice. Conclusion: LIPUS at 25 mW/cm2 itself does not affect brain functions, while physical restraint for LIPUS therapy elicits struggle-like behaviors in the male mice. An unbound helmet targeted with ultrasound intensity at 25-50 mW/cm2 is proposed for clinical brain disease therapy.
Exploring Barriers and Facilitators That Influence Uptake of Oral Pre-Exposure Prophylaxis Among Men Who Have Sex With Men in Bulawayo, Zimbabwe: Key Stakeholder’s Perspectives
Authors: Moyo Perez Livias , Nunu Wilfred Njabulo
Published: January 2024

The world has been on the path to ending HIV and AIDS as a global threat by 2030; despite these efforts, the rate of new HIV infections among men who have sex with men remains very high. This study sought to explore the perceptions of key stakeholders on the potential barriers and facilitators of pre-exposure prophylaxis use among this key population. An exploratory, descriptive (through interviews) qualitative study was conducted on 10 key informants who were purposively selected and snowballed based on their knowledge and experience toward pre-exposure prophylaxis programming among men who have sex with men. The interviews were recorded, transcribed verbatim, coded, and thematically analyzed on MAXQDA. Stated barriers were stigma, lack of information, wrong messaging around pre-exposure prophylaxis, hearing negative things about the pills, the burden of taking pills daily, negative attitudes from health care providers, non-friendly health care facilities, pre-exposure prophylaxis not being affordable, and lack of flexibility and privacy from public hospitals. Identified facilitators were correct messaging on pre-exposure prophylaxis, long-lasting injectable pre-exposure prophylaxis, improved packaging, de-stigmatization, more friendly facilities, differentiated service approach, community groups, engagement, and partnership. To address these barriers and leverage the facilitators, it is imperative to have accessible, affordable services, non-judgmental health care providers, and peer support networks to empower men who have sex with men to make informed decisions regarding their sexual and reproductive health. Continued efforts to remove barriers and promote facilitators are crucial for maximizing the potential of pre-exposure prophylaxis as an effective HIV prevention tool among this population.
A comparison between a gastroesophageal reflux disease questionnaire-based algorithm and multichannel intraluminal impedance-pH monitoring for the treatment of gastroesophageal reflux-induced chronic cough
Authors: Li Wanzhen , Zhang Tongyangzi , Gu Wenhua , Shi Wenbo , Wang Shengyuan , Zhu Yiqing , Shi Cuiqin , Yu Li , Xu Xianghuai
Published: January 2024

Background:

Empiric therapy with multichannel intraluminal impedance-pH monitoring (MII-pH) has been used for the initial treatment of gastroesophageal reflux-induced chronic cough (GERC). However, an algorithm based on the gastroesophageal reflux disease questionnaire (GerdQ) has the potential to achieve a simple, structured, and effective treatment approach for patients with GERC.

Objectives:

This study compared the efficacy of anti-reflux therapy based on GerdQ (new structured pathway, NSP) with medical treatment after MII-pH examination (ordinary clinical pathway, OCP) in the management of GERC.

Design:

For the NSP, we adapted the GerdQ score to establish the basis for a treatment algorithm. For the OCP, treatment was determined using the MII-pH examination results.

Methods:

The non-inferiority (NI) hypothesis was used to evaluate NSP versus OCP.

Results:

Overall, the NSP and OCP-based therapeutic algorithms have similar efficacy for GERC [NI analysis: 95% confidence interval (CI), −4.97 to 17.73, p = 0.009; superiority analysis: p = 0.420]. Moreover, the cough symptom scores and cough threshold improved faster in the NSP group than in the OCP group at week 8 ( p < 0.05). In the subgroup analyses using the GerdQ and GerdQ impact scale (GIS) scores, patients with low-likelihood GERC (GerdQ < 8) were more likely to benefit from OCP (NI analysis: 95% CI, −19.73 to 18.02, p = 0.213). On the other hand, in patients with high-likelihood and low-reflux impact GERC patients (GerdQ > 8 and GIS < 4), the NSP arm was not inferior to the standard treatment of OCP (NI analysis: 95% CI, −8.85 to 28.21%, p = 0.04; superiority analysis: p = 0.339), indicating that GerdQ- and GIS-guided diagnosis and management of patients with GERC could be an alternative to MII-pH management, especially in settings with reduced medical resources.

Conclusions:

The use of the GerdQ algorithm should be considered when handling patients with GERC in the primary care setting.

Trial registration:

This research was registered in the Chinese Clinical Trials Registry (ChiCTR-ODT-12001899).
Evolocumab use in clinical practice in Switzerland: final data of the observational HEYMANS cohort study
Authors: Sudano Isabella , Krähenbühl Stephan , Mach François , Anstett Anne , Dhalwani Nafeesa , Bridges Ian , Sibartie Mahendra , Ray Kausik K.
Published: January 2024

Aims:

The HEYMANS study observed patients receiving evolocumab as part of routine clinical hyperlipidemia management. It was designed to capture data on clinical parameters relevant to health authorities and physicians.

Methods:

This was a European multi-country observational cohort serial chart review study; data on the Swiss cohort are reported here. Patients were prescribed evolocumab as per the Swiss reimbursement criteria in force at the time and were invited chronologically. The study consisted of a 6-month period prior to initiation of evolocumab, a 12-month core observation period (entered by 75 patients, completed by 74 patients), and an 18-month extended observation period (entered by 40 patients, completed by 34 patients). The primary objective was to describe the clinical characteristics of patients receiving evolocumab. Secondary objectives included to describe lipid levels, evolocumab use, and patterns of use of other lipid-lowering therapies (LLT, that is, statins and/or ezetimibe) over time. The study was conducted in the Swiss cohort between May 2017 and June 2021.

Results:

Patients who received evolocumab in Swiss routine practice mostly were in secondary prevention (93%) and had a history of statin intolerance (85%) with 53% receiving no background LLT. One-third had familial hypercholesterolemia. Patients initiated evolocumab at a median low-density lipoprotein cholesterol (LDL-C) of 3.6 mmol/L, which decreased by 54% within 3 months to 1.6 mmol/L and was stable thereafter. Overall, 61% achieved the LDL-C goal of <1.4 mmol/L with more patients attaining this goal when they received evolocumab with a statin and/or ezetimibe (84%) compared to 41% when receiving evolocumab alone. An LDL-C reduction of ⩾50% was achieved by 85% of patients. Persistence with evolocumab at 12 months was 85%.

Conclusion:

In Swiss clinical practice, evolocumab was mainly prescribed to patients with very high cardiovascular risk, who had very high LDL-C levels. Most patients continued to use evolocumab throughout the study period. In these patients, LDL-C was reduced by >50% within 3 months and LDL-C reductions were maintained over time. Guideline-recommended LDL-C goals for this very high-risk cohort were more frequently attained in patients receiving a combination of statin and/or ezetimibe and evolocumab.

Trial registration:

ClinicalTrials.gov Identifier: NCT02770131.
Tenecteplase for the treatment of acute ischemic stroke in the extended time window: a systematic review and meta-analysis
Authors: Palaiodimou Lina , Katsanos Aristeidis H. , Turc Guillaume , Romoli Michele , Theodorou Aikaterini , Lemmens Robin , Sacco Simona , Velonakis Georgios , Vlachopoulos Charalambos , Tsivgoulis Georgios
Published: January 2024

Background:

Outcome data regarding the administration of tenecteplase (TNK) to acute ischemic stroke (AIS) patients presenting in the extended time window are limited.

Objectives:

We aimed to assess the current evidence regarding the efficacy and safety of TNK at a dose of 0.25 mg/kg for AIS treatment in the extended time window.

Design:

A systematic review and meta-analysis was conducted including all available randomized-controlled clinical trials (RCTs) that compared TNK 0.25 mg/kg versus no thrombolysis in AIS patients presenting in the extended time window (>4.5 h after last-seen-well or witnessed onset).

Data sources and methods:

Eligible studies were identified by searching Medline, Scopus, and international conference abstracts. The predefined efficacy outcomes of interest were 3-month excellent functional outcome [defined as the modified Rankin Scale (mRS) score ⩽1; primary outcome], 3-month good functional outcome (mRS ⩽ 2), 3-month reduced disability (⩾1-point reduction across all mRS scores). We determined symptomatic intracranial hemorrhage (sICH), any ICH and 3-month mortality as safety endpoints. A random-effects model was used to calculate risk ratios (RRs) and common odds ratios (cORs) with corresponding 95% confidence intervals (CIs).

Results:

Three RCTs were included comprising 556 patients treated with TNK versus 560 controls. TNK 0.25 mg/kg was associated with a higher likelihood of 3-month excellent functional outcome compared to controls (RR = 1.17; 95% CI = 1.01–1.36; I2 = 0%), whereas there was no difference regarding good functional outcome (RR = 1.05; 95% CI = 0.94–1.17; I2 = 0%) and reduced disability (adjusted cOR = 1.14; 95% CI = 0.92–1.40; I2 = 0%) at 3 months. The risks of sICH (RR = 1.67; 95% CI = 0.70–4.00; I2 = 0%), any ICH (RR = 1.08; 95% CI = 0.90–1.29; I2 = 0%) and 3-month mortality (RR = 1.10; 95% CI = 0.81–1.49; I2 = 0%) were similar between the groups.

Conclusion:

Based on data from three RCTs showing increased efficacy and a favorable safety profile of TNK in the treatment of AIS in the extended time window, continuing efforts of ongoing RCTs in the field are clearly supported.

Trial registration:

PROSPERO registration ID: CRD42023448707.
Educational interventions for promoting sexual and reproductive health in school counselors: a three-arm, randomized control trial comparing lecturing, buzz group and role-play
Authors: Alavi-Arjas Fatemeh , Firouzabadi Maryam , Farnam Farnaz , Balvardi Mohadeseh , Taheri Mahdiye , Riazi Hedyeh , Pourramezani Naimeh , Keshavarz Zohreh
Published: January 2024

Background and objective:

School-based sexual and reproductive health (SRH) education is often reported as being inadequate and/or inconsistent. This study aimed to investigate the educational interventions for promoting SRH in school counselors and compare the results in three groups: lecturing, buzz group and role-play.

Materials and methods:

An intervention quasi-experimental design was employed to evaluate the usefulness of educating SRH topics by using interactive teaching methods for 120 school counselors. Changes in the participants’ knowledge, attitudes and self-efficacy toward SRH education were evaluated by each group using a pretest and a posttest.

Results:

The results of this study revealed that 75% of counselors deemed SRH training vital and felt that the best SRH educators are health care providers and the reason might be their lack of educational skills. They also stated that the most significant barriers to education in schools include concerns about parental feedback and lack of appropriate abilities.

Conclusion:

The present study showed that the use of all three methods (lecturing, buzz groups and role-play) in SRH training improves the level of knowledge, attitude and self-efficacy; although role-play could have been more effective than lecturing in improving counselors’ knowledge.
Migrant workers with COVID-19: a major challenge for Gulf Cooperation Council (GCC) countries to curb the spread of infection
Authors: Nahari Tariq H. , Alkhidir Mohamed A. , Ibrahim Hamza M. , Al Mamun Mohammad
Published: January 2024

The six Gulf Cooperation Council (GCC) countries (Saudi Arabia, the United Arab Emirates, Bahrain, Kuwait, Oman and Qatar) host the majority of the estimated 23 million international migrants working in the Arab states. As the COVID-19 pandemic continues to evolve across the GCC states, the health authorities have reported a considerable number of non-national confirmed COVID-19 cases in the region. In Gulf countries, where more than half of the population are foreigners, migrant workers are more likely to contract and spread the disease due to numerous contributing factors. In this regard, unhygienic and overcrowded living conditions, barriers in accessing national or private health services, challenges in accessing accurate health information related to COVID-19, and lack of facemasks and hand hygiene facilities in their housing camps are the major factors that we identified and discuss in this paper. Moreover, we formulated specific recommendations for relevant authorities to overcome the challenges related to migrant workers during this pandemic situation. Because the migrant workers with COVID-19 infection could subsequently lead to more widespread community transmission, protecting this vulnerable group means reducing the risk of transmission for the entire population. It is essential to include migrant workers in all aspects of the response to COVID-19, such as prevention, detection, access to treatment, and containment measures.
High CTLA-4 transcriptomic expression correlates with high expression of other checkpoints and with immunotherapy outcome
Authors: Krishnamurthy Nithya , Nishizaki Daisuke , Lippman Scott M. , Miyashita Hirotaka , Nesline Mary K. , Pabla Sarabjot , Conroy Jeffrey M. , DePietro Paul , Kato Shumei , Kurzrock Razelle
Published: January 2024

Background:

CTLA-4 impedes the immune system’s antitumor response. There are two Food and Drug Administration-approved anti-CTLA-4 agents – ipilimumab and tremelimumab – both used together with anti-PD-1/PD-L1 agents.

Objective:

To assess the prognostic implications and immunologic correlates of high CTLA-4 in tumors of patients on immunotherapy and those on non-immunotherapy treatments.

Design/methods:

We evaluated RNA expression levels in a clinical-grade laboratory and clinical correlates of CTLA-4 and other immune checkpoints in 514 tumors, including 489 patients with advanced/metastatic cancers and full outcome annotation. A reference population (735 tumors; 35 histologies) was used to normalize and rank transcript abundance (0–100 percentile) to internal housekeeping gene profiles.

Results:

The most common tumor types were colorectal (140/514, 27%), pancreatic (55/514, 11%), breast (49/514, 10%), and ovarian cancers (43/514, 8%). Overall, 87 of 514 tumors (16.9%) had high CTLA-4 transcript expression (⩾75th percentile rank). Cancers with the largest proportion of high CTLA-4 transcripts were cervical cancer (80% of patients), small intestine cancer (33.3%), and melanoma (33.3%). High CTLA-4 RNA independently/significantly correlated with high PD-1, PD- L2, and LAG3 RNA levels (and with high PD-L1 in univariate analysis). High CTLA-4 RNA expression was not correlated with survival from the time of metastatic disease [ N = 272 patients who never received immune checkpoint inhibitors (ICIs)]. However, in 217 patients treated with ICIs (mostly anti-PD-1/anti-PD- L1), progression-free survival (PFS) and overall survival (OS) were significantly longer among patients with high versus non-high CTLA-4 expression [hazard ratio, 95% confidence interval: 0.6 (0.4–0.9) p = 0.008; and 0.5 (0.3–0.8) p = 0.002, respectively]; results were unchanged when 18 patients who received anti-CTLA-4 were omitted. Patients whose tumors had high CTLA-4 and high PD-L1 did best; those with high PD-L1 but non-high CTLA-4 and/or other expression patterns had poorer outcomes for PFS ( p = 0.004) and OS ( p = 0.009) after immunotherapy.

Conclusion:

High CTLA-4, especially when combined with high PD-L1 transcript expression, was a significant positive predictive biomarker for better outcomes (PFS and OS) in patients on immunotherapy.
Combined use of Anlotinib with chemotherapy in patients with advanced ovarian cancer: a real-world cohort study and meta-analysis
Authors: Hong XinYi , Qiu ShanHu , Ding Bo , Xu Hao , Shen Yang
Published: January 2024

Background:

Anlotinib is a novel oral small-molecule receptor tyrosine kinase inhibitor. However, the efficacy and safety of its combined use with chemotherapy remain unclear in patients with advanced ovarian cancer.

Objectives:

To assess the efficacy and safety of the combined use of Anlotinib with chemotherapy in patients with advanced ovarian cancer.

Design:

A multi-center retrospective real-world analysis and a meta-analysis.

Data sources and methods:

We enrolled patients with advanced ovarian cancer who received a combination therapy of Anlotinib and chemotherapy from 15 medical centers. We also searched electronic databases for studies assessing the efficacy and safety of the combined use of Anlotinib with chemotherapy in patients with ovarian cancer. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), and median progression-free survival (mPFS).

Results:

A total of 71 patients, who were predominantly recurrent cases, were included in the real-world study. The ORR and DCR of the included patients were 40.8% and 76.1%, respectively; and their mPFS was 4.6 months. The log-rank test showed that previous antiangiogenic therapy was related to a longer mPFS (p < 0.05). Five studies in total were eligible for meta-analysis. The random-effects meta-analysis model showed that the ORR, DCR, and mPFS were 33.8% [95% confidence interval (CI) 22.7–44.8% from four studies], 90.6% (95% CI 73.6–99.9% from five studies), and 6.6 months (95% CI 4.9–8.4 months from five studies). The most common adverse events were hand-foot syndrome and hypertension.

Conclusion:

The combined use of Anlotinib with chemotherapy showed potential in treating patients with advanced ovarian cancer, with a tolerable safety profile.
The Actin Cytoskeleton as a Regulator of Proteoglycan 4
Authors: Gonzalez-Nolde Sofia , Schweiger Cameron J. , Davis Elizabeth E.R. , Manzoni Thomas J. , Hussein Samer M.I. , Schmidt Tannin A. , Cone Stephanie G. , Jay Gregory D. , Parreno Justin
Published: January 2024

Objective

The superficial zone (SZ) of articular cartilage is responsible for distributing shear forces for optimal cartilage loading and contributes to joint lubrication through the production of proteoglycan 4 (PRG4). PRG4 plays a critical role in joint homeostasis and is chondroprotective. Normal PRG4 production is affected by inflammation and irregular mechanical loading in post-traumatic osteoarthritis (PTOA). THe SZ chondrocyte (SZC) phenotype, including PRG4 expression, is regulated by the actin cytoskeleton in vitro. There remains a limited understanding of the regulation of PRG4 by the actin cytoskeleton in native articular chondrocytes. The filamentous (F)-actin cytoskeleton is a potential node in crosstalk between mechanical stimulation and cytokine activation and the regulation of PRG4 in SZCs, therefore developing insights in the regulation of PRG4 by actin may identify molecular targets for novel PTOA therapies.

Materials and methods

A comprehensive literature search on PRG4 and the regulation of the SZC phenotype by actin organization was performed.

Results

PRG4 is strongly regulated by the actin cytoskeleton in isolated SZCs in vitro. Biochemical and mechanical stimuli have been characterized to regulate PRG4 and may converge upon actin cytoskeleton signaling.

Conclusion

Actin-based regulation of PRG4 in native SZCs is not fully understood and requires further elucidation. Understanding the regulation of PRG4 by actin in SZCs requires an in vivo context to further potential of leveraging actin arrangement to arthritic therapeutics.
Criminalizing Psychopathology in Black Americans: Racial and Gender Differences in the Relationship Between Psychopathology and Arrests
Authors: Brownlow Briana N. , Harmon Kassidie S. , Pek Jolynn , Cheavens Jennifer S. , Moore James L. , Coccaro Emil F.
Published: January 2024

Black Americans are arrested at disproportionate levels compared with White Americans. We sought to understand whether the association between psychopathology and arrest record is equally strong for Black Americans and White Americans, hypothesizing that the association would be stronger for Black Americans. In a sample of adults (age: M = 34.81 years), we found that at the same level of psychopathology severity, emotion dysregulation, and impulsivity, Black Americans ( n = 585) exhibited higher rates of being arrested in adulthood than White Americans ( n = 977). These findings held even when controlling for environmental (e.g., socioeconomic status) and individual (e.g., substance-use history) factors associated with arrests. This suggests that the risk conferred by more severe psychopathology on arrests is stronger for Black Americans than White Americans. Our results highlight how structural racism affects both psychopathology and the carceral system to contribute to the overrepresentation of Black Americans within the criminal justice system.
Navigating Chinese international graduate students’ experiences and mobility during US-China geopolitical tensions
Authors: Hou Minghui
Published: January 2024

International students have played an important role in bolstering the soft power of host countries. However, despite their significant contributions to enhancing soft power, Chinese international graduate students, in particular, have faced a less-than-welcoming environment. As US-China geopolitical tensions grow, we know less about the effects on Chinese international graduate students’ experiences and mobility. Through a phenomenology study of eleven Chinese international graduate students’ narratives, this study draws interrelated theories of soft power and the push-pull model to explore how US-China geopolitical tensions shift Chinese students’ experience and mobility. The findings indicate that Chinese students are changing and have more academic and career options. Chinese students have also encountered stereotypes, xenophobia, and Sinophobia, which might shift their decisions on future mobility.
Aging in Place for Community-Dwelling Older Adults in India: A Qualitative Exploration of Prospects and Challenges
Authors: Thampi Kiran , Mathew Lija Mary
Published: January 2024

As global population ages, “Aging in Place” is prioritized as the top aging strategy for many of the older adults worldwide. India, being a nation that is expected to hold the maximum share of the older adult population in the near future, has a huge responsibility vested in it to take care of the needs of older adults. The social structure of the nation has emphasized the importance of older adults to age in place, experiencing all the independence and autonomy at their own dwelling places for as long as possible. This study aims to provide a profound understanding of the meaning, attitude, and perceptions of older adults toward aging in place. Using a qualitative research design, in-depth interviews were conducted among 15 community-dwelling older adults who chose aging in place in Kerala, India. Following the interviews, thematic network analysis was done, inspired by Jennifer Attride-Stirling. Three global themes were derived, which include the older adults’ perspectives on (1) determinants of aging in place, (2) challenges of aging in place, and (3) strategies for successful aging in place. The study evokes in-depth exploration of the experiences of older adults aging in place, which inform future evidence-based practices and policy-level implications.
Operating Under Stress: An Experiential Exercise to Illustrate the Sources and Consequences of Work Stress
Authors: Frieder Rachel E.
Published: January 2024

This experiential exercise is crafted around the classic board game Operation® (Hasbro 2008). Students are instructed that they are members of an emergency room team responsible for curing their patient of their ailments. However, unlike the board game, students in roles of doctors, nurses, and chief of surgery grapple with numerous sources of work-related challenge and hindrance stressors while trying to complete their job duties. In addition, participants are intermittently exposed to various types of work and non–work-related stressors throughout the exercise that cause interruptions to job fulfillment. These various conditions serve to illuminate the sources of job stress as well as the implications of both challenge and hindrance stressors on critical workplace outcomes, such as motivation, satisfaction, and workplace performance. This experiential exercise can be expanded to incorporate several organizational behavior topics, such as justice/fairness, leadership, teamwork, and work redesign.
Functional outcome improvement from 3 to 12 months after intracerebral hemorrhage
Authors: Morotti Andrea , Nawabi Jawed , Pilotto Andrea , Toffali Maddalena , Busto Giorgio , Mazzacane Federico , Cavallini Anna , Laudisi Michele , Gentile Luana , Viola Maria Maddalena , Schlunk Frieder , Bartolini Diletta , Paciaroni Maurizio , Magoni Mauro , Bassi Chiara , Simonetti Luigi , Fainardi Enrico , Casetta Ilaria , Zini Andrea , Padovani Alessandro
Published: January 2024

Introduction:

Most intracerebral hemorrhage (ICH) trials assessed outcome at 3 months but the recovery trajectory of ICH survivors may continue up to 1 year after the index event. We aimed to describe the predictors of functional outcome improvement from 3 to 12 months after ICH.

Materials and Methods:

Retrospective analysis of patients admitted to six European Stroke Centers for supratentorial ICH. Functional outcome was measured with the modified Rankin Scale (mRS) at 3 and 12 months. Predictors of functional outcome improvement were explored with binary logistic regression.

Results:

We included 703 patients, of whom 245 (34.9%) died within 3 months. Among survivors, 131 (28.6%) had an mRS improvement, 78 (17.0%) had a worse mRS and 249 (54.4%) had a stable functional status at 12 months. Older age and the presence of baseline disability (defined as pre-stroke mRS > 1), were associated with lower odds of functional outcome improvement (Odds Ratio (OR) 0.98 per year increase, 95% Confidence Interval (CI) 0.96–1.00, p = 0.017 and OR 0.45, 95% CI 0.25–0.81, p = 0.008 respectively). Conversely, deep ICH location increased the probability of long term mRS improvement (OR 1.67, 95% CI, 1.07–2.61, p = 0.023). Patients with mild-moderate disability at 3 months (mRS 2–3) had the highest odds of improvement at 12 months (OR 8.76, 95% CI 3.68–20.86, p < 0.001).

Discussion and Conclusion:

Long term recovery is common after ICH and associated with age, baseline functional status, mRS at 3 months and hematoma location. Our findings might inform future trials and improve long-term prognostication in clinical practice.
Coping in patients with hematologic malignancies undergoing hematopoietic cell transplantation
Authors: Newcomb Richard , Amonoo Hermioni L. , Nelson Ashley M. , Choe Joanna , Holmbeck Katherine , Nabily Anisa , Lee Stephanie J. , LeBlanc Thomas W. , El-Jawahri Areej
Published: January 2024

Patients undergoing hematopoietic cell transplantation (HCT) must cope with physical and psychological symptoms. Yet, studies examining pre-HCT coping are limited. We aimed to characterize pre-HCT coping, evaluate the association of coping with baseline quality of life (QOL) and psychological distress, and identify sociodemographic factors associated with pre-HCT coping. We conducted a cross-sectional analysis of baseline data from a multisite randomized supportive care intervention trial among patients with hematologic malignancies undergoing allogeneic or autologous HCT. We assessed patient-reported QOL, psychological distress, and coping within 72 hours of admission for HCT. We used the median split method to dichotomize coping and multivariate regression analyses to characterize the association of coping with psychological distress and QOL. Of patients awaiting HCT (n = 360; mean age, 55.4 years; 49.7% autologous), 43.5% were high users of approach-oriented coping, whereas 31.3% were high users of avoidant coping. Patients reported high use of emotional support (60.9%), acceptance (51.2%), self-blame (33%), and denial (31.3%). Older age (≥65 years) was associated with less frequent use of avoidant coping (odds ratio, 0.5; P = .01). Approach-oriented coping was associated with better pre-HCT QOL (Beta(B) = 6.7; P = .001), and lower depression (B = −1.1; P = .001) and anxiety (B = −0.9; P = .02) symptoms. Avoidant coping was associated with worse pre-HCT QOL (B = −13.3; P < .001) and symptoms of depression (B = 1.9; P < .001), anxiety (B = 3.1; P < .001), and posttraumatic stress disorder (B = 8.1; P < .001). Pre-HCT coping is strongly associated with psychological distress and QOL. These data support the need for interventions to address coping during HCT hospitalization. This clinical trial was registered at www.clinicaltrials.gov as #NCT03641378.
Reprogramming of pyrimidine nucleotide metabolism supports vigorous cell proliferation of normal and malignant T cells
Authors: Watanabe Tatsuro , Yamamoto Yuta , Kurahashi Yuki , Kawasoe Kazunori , Kidoguchi Keisuke , Ureshino Hiroshi , Kamachi Kazuharu , Yoshida-Sakai Nao , Fukuda-Kurahashi Yuki , Nakamura Hideaki , Okada Seiji , Sueoka Eisaburo , Kimura Shinya
Published: January 2024

Adult T-cell leukemia/lymphoma (ATL) is triggered by infection with human T-cell lymphotropic virus-1 (HTLV-1). Here, we describe the reprogramming of pyrimidine biosynthesis in both normal T cells and ATL cells through regulation of uridine-cytidine kinase 2 (UCK2), which supports vigorous proliferation. UCK2 catalyzes the monophosphorylation of cytidine/uridine and their analogues during pyrimidine biosynthesis and drug metabolism. We found that UCK2 was overexpressed aberrantly in HTLV-1–infected T cells but not in normal T cells. T-cell activation via T-cell receptor (TCR) signaling induced expression of UCK2 in normal T cells. Somatic alterations and epigenetic modifications in ATL cells activate TCR signaling. Therefore, we believe that expression of UCK2 in HTLV-1–infected cells is induced by dysregulated TCR signaling. Recently, we established azacitidine-resistant (AZA-R) cells showing absent expression of UCK2. AZA-R cells proliferated normally in vitro, whereas UCK2 knockdown inhibited ATL cell growth. Although uridine and cytidine accumulated in AZA-R cells, possibly because of dysfunction of pyrimidine salvage biosynthesis induced by loss of UCK2 expression, the amount of UTP and CTP was almost the same as in parental cells. Furthermore, AZA-R cells were more susceptible to an inhibitor of dihydroorotic acid dehydrogenase, which performs the rate-limiting enzyme of de novo pyrimidine nucleotide biosynthesis, and more resistant to dipyridamole, an inhibitor of pyrimidine salvage biosynthesis, suggesting that AZA-R cells adapt to UCK2 loss by increasing de novo pyrimidine nucleotide biosynthesis. Taken together, the data suggest that fine-tuning pyrimidine biosynthesis supports vigorous cell proliferation of both normal T cells and ATL cells.
Bioaccessibility-corrected probabilistic health risk assessment of dietary metal(loid) exposure in six major food groups in children from Northwest China
Authors: Wang Beibei , Zhang Liwen , Feng Weiying , Zhang Han , Duan Xiaoli , Qin Ning
Published: January 2024

Dietary exposure to heavy metals and metalloids [metal(loid)s] deserves increased attention; however, there is a lack of a comprehensive understanding of the risks of dietary exposure from multi-type food intake and multi-metal(loid) exposure using a bioaccessibility-corrected method. Here, we determined the concentration and bioaccessibility of six toxic metal(loid)s in six major food groups in an industrial city with intensive smelting activity. By incorporating children’s dietary patterns, the probability distribution of health risks from dietary metal(loid)s exposure was assessed. Marked differences were observed in the dietary exposure characteristics within metal(loid)s and major food groups. Cereal and vegetables were the major food groups local children intake. Cereals, meat, beans, and aquatic products had the highest concentrations of Cu and Cd, Pb and Cr, Ni, and As, respectively. Generally, meat, eggs, and aquatic products exhibited higher bioaccessibility than cereals, beans, and vegetables. The bioaccessibility of metal(loid)s decreased in the following order: Pb > Cr > Cu > Ni > As > Cd. For non-carcinogenic risks, the average hazard index was 7.3, with 99.6% exceeding acceptable levels. Arsenic was the dominant risk element and aquatic product was the main risk source. The aggregated carcinogenic risk was 3.4 × 10–3, with Cr the major risk contributor and cereals and meat the dominant food sources. The findings demonstrated that (1) the metal(loid) dietary exposure risk of children from areas with intensive smelting activities should be taken seriously, and (2) it is necessary to identify the specific food category and metal(loid) based on a comprehensive analysis of the metal(loid) concentration and bioaccessibility, and dietary habits of the population to effectively reduce risk.
GIS-based multi-influencing factor (MIF) application for optimal site selection of solar photovoltaic power plant in Nashik, India
Authors: Rane Nitin Liladhar , Günen Mehmet Akif , Mallick Suraj Kumar , Rane Jayesh , Pande Chaitanya B. , Giduturi Monica , Bhutto Javed Khan , Yadav Krishna Kumar , Tolche Abebe Debele , Alreshidi Maha Awjan
Published: January 2024

The significant natural energy sources for reducing the global usage of fossil fuels are renewable energy (RE) sources. Solar energy is a crucial and reliable RE source. Site selection for solar photovoltaic (PV) farms is a crucial issue in terms of spatial planning and RE policies. This study adopts a Geographic Information System (GIS)-based Multi-Influencing Factor (MIF) technique to enhance the precision of identifying and delineating optimal locations for solar PV farms. The choice of GIS and MIF is motivated by their ability to integrate diverse influencing factors, facilitating a holistic analysis of spatial data. The selected influencing factors include solar radiation, wind speed, Land Surface Temperature (LST), relative humidity, vegetation, elevation, land use, Euclidean distance from roads, and aspect. The optimal sites of solar PV power plant delineated revealed that ‘very low’ suitability of site covering 4.866% of the study area, ‘low’ suitability of site 13.190%, ‘moderate’ suitability of site 31.640%, ‘good’ suitability of site 32.347%, and ‘very good’ suitability of site for solar PV power plant encompassing 17.957% of the study area. The sensitivity analysis results show that the solar radiation, relative humidity, and elevation are the most effective on the accuracy of the prediction. The validation of the results shows the accuracy of solar PV power plant prediction using MIF technique in the study area was 81.80%. The integration of GIS and MIF not only enhances the accuracy of site suitability assessment but also provides a practical implementation strategy. This research offers valuable insights for renewable energy policymakers, urban planners, and other stakeholders seeking to identify and develop optimal locations for solar energy power farms in their respective regions.
Novel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with PD-1 and PD-L1 aptamers
Authors: Jiang Qiping , Yao Fengjiao , An Yacong , Lai Xialian , Li Xundou , Yu Zhen , Yang Xian-Da
Published: January 2024

Background

PD-1/PD-L1 blockade plays a crucial role in cancer immunotherapy. Exploration of new technologies to further enhance the efficacy of PD-1/PD-L1 blockade is therefore of potential medical importance. Nanotherapeutics can accumulate in tumor tissues due to enhanced permeability and retention (EPR) effects. In this study, a novel nanotherapeutic for cancer immunotherapy was implemented with albumin nanoparticles functionalized by both PD-1 and PD-L1 aptamers.

Results

Albumin nanoparticles (NP) were functionalized with either PD-1 aptamers (PD1-NP), PD-L1 aptamers (PDL1-NP), or both types of aptamers (PD1-NP-PDL1). Average sizes of PD1-NP, PDL1-NP, and PD1-NP-PDL1 were 141.8 nm, 141.8 nm, and 164.2 nm, respectively. PD1-NP had good affinity for activated T cells that expresses PD-1. Similarly, PDL1-NP could bind with MDA-MB-231 or CT26 tumor cells that express PD-L1. Moreover, the bispecific PD1-NP-PDL1 could bind with both the activated T cells and the PD-L1-expressing tumor cells, and tether the two type of cells together. Functionally, aptamer-modified nanoparticles exhibited stronger immune-stimulating effects vs. free aptamers. Specifically, PD1-NP or PDL1-NP induced stronger lymphocyte-mediated cytotoxicity against PD-L1-expressing tumor cells in vitro vs. free PD-1 or PD-L1 aptamers. Animal studies also showed that PD1-NP or PDL1-NP significantly improved antitumor efficacy against CT26 colon cancer in vivo vs. free PD-1 or PD-L1 aptamers. Importantly, the bispecific PD1-NP-PDL1 further boosted the in vivo antitumor efficacy compared with PD1-NP or PDL1-NP, without raising systemic toxicity.

Conclusion

The results suggest that the bispecific PD1-NP-PDL1 is a promising nanotherapeutic to improve the efficacy of PD-1/PD-L1 blockade, and may have application potential in colon cancer treatment.