bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity, Psychological Distress, and Resting State Connectivity of the Hippocampus and Amygdala Among Women With Early-Stage Breast Cancer
Authors: Donofry Shannon D. , Lesnovskaya Alina , Drake Jermon A. , Ripperger Hayley S. , Gilmore Alysha D. , Donahue Patrick T. , Crisafio Mary E. , Grove George , Gentry Amanda L. , Sereika Susan M. , Bender Catherine M. , Erickson Kirk I. 
Published: April 2022

ObjectiveOverweight and obesity [body mass index (BMI) ≥ 25 kg/m2] are associated with poorer prognosis among women with breast cancer, and weight gain is common during treatment. Symptoms of depression and anxiety are also highly prevalent in women with breast cancer and may be exacerbated by post-diagnosis weight gain. Altered brain function may underlie psychological distress. Thus, this secondary analysis examined the relationship between BMI, psychological health, and resting state functional connectivity (rsFC) among women with breast cancer.MethodsThe sample included 34 post-menopausal women newly diagnosed with Stage 0-IIa breast cancer (Mage = 63.59 ± 5.73) who were enrolled in a 6-month randomized controlled trial of aerobic exercise vs. usual care. At baseline prior to randomization, whole-brain analyses were conducted to evaluate the relationship between BMI and seed-to-voxel rsFC of the hippocampus and amygdala. Connectivity values from significant clusters were then extracted and examined as predictors of self-reported depression and anxiety.ResultsMean BMI was in the obese range (M = 31.83 ± 6.62). For both seeds examined, higher BMI was associated with lower rsFC with regions of prefrontal cortex (PFC), including ventrolateral PFC (vlPFC), dorsolateral PFC, and superior frontal gyrus (z range = 2.85–4.26). Hippocampal connectivity with the vlPFC was negatively correlated with self-reported anxiety (β = 0.47, p &lt; 0.01).ConclusionHigher BMI was associated with lower hippocampal and amygdala connectivity to regions of PFC implicated in cognitive control and emotion regulation. BMI-related differences in hippocampal and amygdala connectivity following a recent breast cancer diagnosis may relate to future worsening of psychological functioning during treatment and remission. Additional longitudinal research exploring this hypothesis is warranted.
Effect of Moderate-to-Severe Iodine Deficiency in Early Pregnancy on Subclinical Hypothyroidism: A Longitudinal Study in an Iodine-Sufficient Region in China
Authors: Wang Taotao , Liu Yanqiu , Kong Qianqian , Cao Xiaoxia , Liu Yuzhou , Xia Song , Zheng Tingting , Yu Li 
Published: April 2022

ObjectiveTo investigate iodine status among pregnant women in an iodine-sufficient region in China after the implementation of revised universal salt iodization (USI) standards in 2012 and assess the association between urinary iodine concentrations (UIC) in early pregnancy and the incidence of subclinical hypothyroidism (SCH) in euthyroid women negative for antithyroid Ab during different trimesters.MethodsWe measured the iodine status of 1,264 pregnant women, and performed follow-up assessment of thyroid function at 20 and 30 weeks of gestation among a cohort of 250 euthyroid women. We assessed the association of UIC in the 1st trimester with the incidence of SCH in subsequent trimesters. UIC and serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured.ResultsThe median UIC was 135.95 μg/L among 1,264 women. Serum FT4 level was significantly higher in the group of UIC 150 to 249 μg/L compared with other UIC groups (P &lt; 0.001). TSH was significantly higher in the UIC more than or equal to 250 μg/L group than the UIC 150 to 249 g/L group (P = 0.043). Of the 250 euthyroid women negative for antithyroid Ab (TSH value of 2.5–3.55 mU/L) in the 1st trimester, pregnant women with UIC lower than 100 μg/L in the 1st trimester exhibited a significantly increased risk of SCH (odds ratio [OR] = 2.47; 95% confidence interval [CI] = 1.22–5.71; P = 0.012, according to the Chinese Medical Association criteria; OR = 5.22, 95% CI = 1.73–6.09, P = 0.004, according to ATA criteria) during the latter half of pregnancy compared with the UIC 150 to 249 μg/L group.ConclusionModerate-to-severe iodine deficiency (UIC lower than 100 μg/L) in the 1st trimester was associated with a significantly higher risk of SCH during the 2nd or 3rd trimesters among euthyroid pregnant women who had negative for antithyroid Ab. Women with SCH during pregnancy require regular UIC tests to maintain appropriate iodine status.
Association of Modified Geriatric Nutrition Risk Index and Handgrip Strength With Survival in Cancer: A Multi-Centre Cohort Study
Authors: Xie Hailun , Ruan Guotian , Zhang Heyang , Zhang Qi , Ge Yizhong , Song Mengmeng , Zhang Xi , Lin Shiqi , Liu Xiaoyue , Liu Yuying , Zhang Xiaowei , Li Xiangrui , Zhang Kangping , Yang Ming , Tang Meng , Li Zengning , Shi Hanping 
Published: April 2022

BackgroundThis study aimed to explore the value of combining the modified geriatric nutrition risk index (mGNRI) and handgrip strength (HGS) in the prognosis assessment of cancer.MethodsThis multicenter, prospective cohort study, enrolled 5,607 cancer patients from 27 medical centers across 17 provinces in China between June 2012 and December 2019. The primary outcome was overall survival. Secondary outcomes included the Karnofsky Performance Scale (KPS) score, Patient-Generated Subjective Global Assessment (PG-SGA) score, cachexia, and admission 90-day outcome. A composite prognostic score (mGNRI-HGS score) was developed based on the mGNRI and HGS. The Kaplan–Meier method was used to draw the survival curve, and log-rank analysis was used to estimate the survival rate. The Cox proportional hazards model was used to investigate the associations of the mGNRI, HGS or mGNRI-HGS score with risk of mortality among the cancer patients, adjusted for potential confounders.ResultsA low mGNRI (HR = 0.99, 95%CI = 0.98–0.99, p &lt; 0.001) and low HGS (HR = 0.99, 95%CI = 0.98–0.99, p = 0.001) were associated with an increased risk of mortality. A severe mGNRI-HGS score was independently associated with reduced survival. Compared with patients with normal scores, the risk of mortality among the patients with moderate and severe mGNRI-HGS scores was 28.8 and 13.3% higher, respectively. Even within the same pathological stage, it presented significant gradient prognostic stratification. Additionally, a low mGNRI-HGS score was also independently associated with a higher risk of low KPS (p &lt; 0.001), high PGSGA (p &lt; 0.001), cachexia (p &lt; 0.001), and adverse admission 90-day outcome (p &lt; 0.001).ConclusionsThe mGNRI and HGS may be useful predictors of long-term prognosis in cancer patients. The combination of the two methods provides effective prognostic stratification for cancer patients and could predict physical frailty, malnutrition, and cachexia.
Accurate Prediction of Metachronous Liver Metastasis in Stage I-III Colorectal Cancer Patients Using Deep Learning With Digital Pathological Images
Authors: Xiao Chanchan , Zhou Meihua , Yang Xihua , Wang Haoyun , Tang Zhen , Zhou Zheng , Tian Zeyu , Liu Qi , Li Xiaojie , Jiang Wei , Luo Jihui 
Published: April 2022

ObjectivesMetachronous liver metastasis (LM) significantly impacts the prognosis of stage I-III colorectal cancer (CRC) patients. An effective biomarker to predict LM after surgery is urgently needed. We aimed to develop deep learning-based models to assist in predicting LM in stage I-III CRC patients using digital pathological images.MethodsSix-hundred eleven patients were retrospectively included in the study and randomly divided into training (428 patients) and validation (183 patients) cohorts according to the 7:3 ratio. Digital HE images from training cohort patients were used to construct the LM risk score based on a 50-layer residual convolutional neural network (ResNet-50). An LM prediction model was established by multivariable Cox analysis and confirmed in the validation cohort. The performance of the integrated nomogram was assessed with respect to its calibration, discrimination, and clinical application value.ResultsPatients were divided into low- and high-LM risk score groups according to the cutoff value and significant differences were observed in the LM of the different risk score groups in the training and validation cohorts (P&lt;0.001). Multivariable analysis revealed that the LM risk score, VELIPI, pT stage and pN stage were independent predictors of LM. Then, the prediction model was developed and presented as a nomogram to predict the 1-, 2-, and 3-year probability of LM. The integrated nomogram achieved satisfactory discrimination, with C-indexes of 0.807 (95% CI: 0.787, 0.827) and 0.812 (95% CI: 0.773, 0.850) and AUCs of 0.840 (95% CI: 0.795, 0.885) and 0.848 (95% CI: 0.766, 0.931) in the training and validation cohorts, respectively. Favorable calibration of the nomogram was confirmed in the training and validation cohorts. Integrated discrimination improvement and net reclassification index indicated that the integrated nomogram was superior to the traditional clinicopathological model. Decision curve analysis confirmed that the nomogram has clinical application value.ConclusionsThe LM risk score based on ResNet-50 and digital HE images was significantly associated with LM. The integrated nomogram could identify stage I-III CRC patients at high risk of LM after primary colectomy, so it may serve as a potential tool to choose the appropriate treatment to improve the prognosis of stage I-III CRC patients.
The Therapeutic Effect and Clinical Outcome of Immune Checkpoint Inhibitors on Bone Metastasis in Advanced Non-Small-Cell Lung Cancer
Authors: Asano Yohei , Yamamoto Norio , Demura Satoru , Hayashi Katsuhiro , Takeuchi Akihiko , Kato Satoshi , Miwa Shinji , Igarashi Kentaro , Higuchi Takashi , Yonezawa Hirotaka , Araki Yoshihiro , Morinaga Sei , Saito Shiro , Sone Takashi , Kasahara Kazuo , Tsuchiya Hiroyuki 
Published: April 2022

IntroductionIn advanced non-small-cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs) have been reported a better treatment outcome on primary lesions, however, the therapeutic effect on bone metastases has not been clarified. This study investigates the therapeutic effect of ICIs on bone metastases in advanced NSCLC.MethodsThe data of patients with advanced NSCLC, treated with ICIs from 2016 to 2019 at our hospital, were analyzed. The therapeutic effects of ICIs on primary lung and metastatic bone lesions, concomitant use of bone modifying agents (BMA), treatment outcomes, and frequency of immune-related adverse events (irAEs) and skeletal-related events (SREs) were investigated.ResultsA total of 29 patients were included (19 men and 10 women; mean age, 64.2 years). Among the ICIs, pembrolizumab was the most used (55.2%), and concomitant use of BMA was prevalent in 21 patients (zoledronic acid=1, denosumab=20). The therapeutic effect was partial response (PR) in 10.3% (n=3) on primary lung lesions by RECIST 1.1, complete response (CR) in 6.9% (n=2) and PR in 17.2% (n=5) on bone metastatic lesions by MDA criteria. ICIs suppressed the progression of bone metastasis in 21 cases (72.4%). All patients in CR and PR were treated with pembrolizumab and denosumab. SREs and irAEs were developed in 3.4% (n=1) and 20.7% (n=6), respectively. The median survival time after treatment with ICIs was 11.0 months. Concomitant therapy with ICIs and denosumab significantly prolonged the overall survival compared to ICI-only therapy (16.0 months vs. 2.5 months, p&lt;0.01).ConclusionsThis study showed that treatment with ICIs may successfully suppress the progression of bone metastasis in advanced NSCLC. Pembrolizumab with denosumab had the highest therapeutic effect on both primary lung lesions and bone metastases. Systemic treatment with this combination and conservative treatment of bone metastasis could be one of the options in the treatment of advanced NSCLC.
Access to Insulin Products in Pakistan: A National Scale Cross-Sectional Survey on Prices, Availability, and Affordability
Authors: Saeed Amna , Lambojon Krizzia , Saeed Hamid , Saleem Zikria , Anwer Naveed , Aziz Muhammad Majid , Ji Wenjing , Liu Wenchen , Chen Chen , Yang Caijun , Fang Yu , Babar Zaheer-Ud-Din 
Published: April 2022

Background: Diabetes is among the top ten most prevalent diseases in Pakistan, and the availability of medicines to treat the disease is vital for a great percentage of the country’s population. Insulin was discovered a century ago; however, its access in several parts of the globe remains an issue. This study aims to evaluate prices, availability, and affordability (access components) of insulin and five comparator medicine access in Pakistan.Methods: A nationwide cross-sectional survey was conducted to evaluate the access to insulin and some comparator medicines in eight cities of Pakistan, using a modified WHO/HAI methodology. The survey included 80 medicine outlets, i.e., 40 private pharmacies and 40 public hospitals. Data for every unique insulin product available in the Pakistani market were obtained, including five comparator medicines. Percentage availability, median unit prices (MUPs), and affordability (the number of days’ wages (NDWs) required for a month’s course by the lowest-paid unskilled government worker) of all products were calculated, including originator brands (OBs) and biosimilar (BS) products.Results: Of all insulin products surveyed (n = 320), 87.5% were manufactured by foreign multinational companies (MNCs). None of the insulin products had an ideal availability of 80% in any of the surveyed health facilities. In the public sector, none of the insulin products had an availability of more than 50%. In the public sector, the overall availability of human insulin was 70% (including OB and BS). While in the private sector, the overall availability of human insulin was 90% and that of analog insulin was 62.5%. The analog insulin products were 72.8% costlier than the human insulin products. The median prices of BS insulin were 25.4% lower than the OB products, indicating that almost one-fourth of the cost could be saved by switching to BS human insulin from OB human insulin. All oral anti-diabetic medicines were found to be affordable, whereas none of the insulin was affordable. The NDWs for human and analog insulin were 1.38 and 5.06.Conclusion: In Pakistan, the insulin availability falls short of the WHO’s benchmark of 80%. Insulin continues to be unaffordable in both private and government sectors. To increase insulin access, the government should optimize insulin procurement at all levels, promote local production, enforce biosimilar prescribing, and provide financial subsidies for these products.
Precipitation Patterns in Reaction–Diffusion–Reaction Systems of Prussian Blue and Cu–Fe-Based Prussian Blue Analogs
Authors: Hayashi Hisashi 
Published: April 2022

In agarose gel containing [Fe(CN)6]3‒ions and sandwiched between two metal rods (Ti, Fe, or Cu) with a voltage of 1‒5 V applied for 20–100 h, reaction–diffusion–reaction (RDR) processes (that is, electrochemical reactions at metal rods to generate reactant ions, diffusion of the reactant ions influenced by the electric field in agarose gel, and reactions of the reactant ions to form/decompose precipitates) were coupled to generate diverse precipitation patterns of Prussian blues (PB) or Cu–Fe-based Prussian blue analogs (Cu–Fe PBA). These patterns strongly depended on the type of metal electrode, applied voltage, initial [Fe(CN)6]3‒concentration, and elapsed time after voltage application. Under the application of 2 V for 20/50 h, the PB/Cu–Fe PBA formed a discrete precipitation band on the anode/cathode side in an agarose gel containing 0.050 M [Fe(CN)6]3‒ions. In the Cu–Fe PBA system, a relatively long precipitation band of Cu(OH)2was also generated on the anode side by OH−ions produced on the cathode as a byproduct. Longer voltage applications promoted propagation of the Cu–Fe PBA band to the anode side and caused the discrete PB band to disappear. Higher initial [Fe(CN)6]3‒concentrations deepened the color of the generated patterns. Higher voltage applications suppressed the propagation of the Cu–Fe PBA band to the anode side and caused the PB band to disappear. Experiments using a Ti cathode suggested that the formation and subsequent decomposition of PB or Cu–Fe PBA at the cathode surface are important for forming precipitation band(s) in the gel near the cathode. The application of cyclic alternating voltages (particularly, 4 V for 1 h and 1 V for 4 h) was effective in generating Liesegang-band-like periodic bands, particularly for the Cu–Fe PBA system.
Blocking Intermediate-Conductance Calcium-Activated Potassium Channels in the Macrophages Around Ganglionated Plexi Suppresses Atrial Fibrillation Vulnerability in Canines With Rapid Atrial Pacing
Authors: Ma Yazhe , Fu Yuntao , Wang Youcheng , Yang Mei , Yao Yajun , He Shanqing , Liu Dishiwen , Cao Zhen , Wang Xi , Tang Yanhong , Zhao Qingyan , Huang Congxin 
Published: April 2022

Previous studies have indicated that ganglionated plexi (GP) function influences atrial fibrillation (AF) vulnerability, and intermediate-conductance calcium-activated potassium channels (SK4) have a close relationship with cardiomyocyte automaticity and the induction of AF. However, the effects of the SK4 inhibitor on GP function and AF vulnerability are unknown. Eighteen beagles were randomly divided into a control group (n = 6), rapid atrial pacing (RAP) group (n = 6), and triarylmethane-34 (TRAM-34, an SK4 inhibitor) group (n = 6). TRAM-34 (0.3 ml, 15 mmol/L) and saline were locally injected into GPs in the TRAM-34 group dogs and dogs from the other groups, respectively. After that, dogs in the RAP and TRAM-34 groups were subjected to RAP, and the neural activity of anterior right GP (ARGP) and atrial electrophysiology were measured. The levels of inflammatory cytokines and function of macrophages in the ARGP were measured in the three groups. At 10 min after TRAM-34 injection, ARGP activity and atrial electrophysiology did not significantly change. The atrial pacing shortened effective refractory period (ERP) values at all sites and increased the AF vulnerability and ARGP neural activity, while TRAM-34 reversed these changes. The levels of CD68 + cells, induced nitric oxide synthase (iNOS), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the ARGP tissues were higher in the RAP group and TRAM-34 group than they were in the control group. Furthermore, the levels of the CD68 + cells, iNOS, and inflammatory cytokines in the ARGP tissues were higher in the pacing group than those in the TRAM-34 group. Based on these results, administration of TRAM-34 into the atrial GP can suppress GP activity and AF vulnerability during atrial pacing. The effects of TRAM-34 might be related to macrophage polarization and the inflammatory response of GP.
Development and Psychometric Evaluation of Family Caregivers’ Hardiness Scale: A Sequential-Exploratory Mixed-Method Study
Authors: Hosseini Lida , Sharif Nia Hamid , Ashghali Farahani Mansoureh 
Published: April 2022

ObjectiveCaring for patients with Alzheimer’s disease (AD) is a stressful situation and an overwhelming task for family caregivers. Therefore, these caregivers need to have their hardiness empowered to provide proper and appropriate care to these older adults. From the introduction of the concept of hardiness, few studies have been conducted to assess the hardiness of caregivers of patients with AD. Presumably, one reason for this knowledge gap is the lack of a proper scale to evaluate hardiness in this group. This study was conducted to develop a reliable and valid Family Caregivers’ Hardiness Scale (FCHS) to measure this concept accurately among Iranian family caregivers sample.MethodsThis study is a cross-sectional study with a sequential-exploratory mixed-method approach. The concept of family caregivers’ hardiness was clarified using deductive content analysis, and item pools were generated. In the psychometric step, the samples were 435 family caregivers with a mean age of 50.26 (SD ± 13.24), and the data were gathered via an online form questionnaire. In this step, the items of the FCHS were evaluated using face and content validity. Then, the factor structure was determined and confirmed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) followed by convergent and divergent validity, respectively. Finally, scale reliability, including stability, and internal consistency were evaluated.ResultsThe finding revealed that FCHS consists of five factors, namely, “Religious Coping” (5 items), “Self-Management” (6 items), “Empathic Communication” (3 items), “Family Affective Commitment” (3 items), and “Purposeful Interaction” (4 items) that explained 58.72% of the total variance. The results of CFA showed a good model fit. Reliability showed acceptable internal consistency and stability.ConclusionBased on the results of the psychometric evaluation of the FCHS, turned out that the concept of hardiness in Iranian family caregivers is a multidimensional concept that is most focused on individual-cultural values, emotional family relationships, and social relationships. The designed scale also has acceptable validity and reliability features that can be used in future studies to measure this concept in family caregivers.
Knowledge, Attitudes, and Practices Toward Coronavirus and Associated Anxiety Symptoms Among University Students: A Cross-Sectional Study During the Early Stages of the COVID-19 Pandemic in Bangladesh
Authors: Patwary Muhammad Mainuddin , Disha Asma Safia , Bardhan Mondira , Haque Md. Zahidul , Kabir Md. Pervez , Billah Sharif Mutasim , Hossain Md. Riad , Alam Md. Ashraful , Browning Matthew H. E. M. , Shuvo Faysal Kabir , Piracha Awais , Zhao Bo , Swed Sarya , Shah Jaffer , Shoib Sheikh 
Published: April 2022

BackgroundUniversity students’ knowledge, attitude, and practice (KAP) toward COVID-19 are vital to prevent the spread of the virus, especially in the context of developing countries. Consequently, the present study aimed to determine the KAP levels of university students and associated anxiety during the earlier stage of the pandemic in Bangladesh.MethodsA cross-sectional, online study with 544 university students was conducted during April 17–May 1, 2020. The questionnaire incorporated several KAP-related test items aligned with the World Health Organization (WHO) guidelines. Anxiety was measured with the 2-item Generalized Anxiety Disorder scale (GAD-2). Multivariable logistic regression analysis was performed to determine the association between KAP levels and anxiety adjusting for sociodemographic variables. Subgroup analyses included rerunning models stratified by gender and quarantine status.ResultsApproximately 50% of students showed high levels of knowledge about COVID-19 guidelines, 59% reported behavioral practices that aligned with COVID-19 guidelines, and 39% had negative attitudes toward COVID-19 guidelines. Attitudes differed by anxiety (χ2 = 23.55, p &lt; 0.001); specifically, negative attitudes were associated with higher anxiety (OR: 2.40, 95% CI = 1.66–3.46, p &lt; 0.001). Associations were significant for male (OR = 2.36; 95% CI = 1.45–3.84, p &lt; 0.001) and female (OR = 2.45; 95% CI = 1.3–4.34; p &lt; 0.001) students. Stratified analyses found non-quarantined students with negative attitudes had three times the chance of experiencing anxiety (OR = 3.14, 95% CI: 1.98–4.98, p &lt; 0.001). Non-quarantined students with low levels of knowledge had half the chance of developing anxiety (OR = 0.49, 95% CI: 0.31–0.78, p &lt; 0.01).ConclusionBased on these findings, it is recommended that university authorities continue to prioritize proactive and effective measures to develop higher levels of knowledge, more positive attitudes and better behavioral practices regarding COVID-19 for the mental health of their students.