bluuebunny/crossref_metadata_2025 huggingface dataset:
A microfluidic system that replicates pharmacokinetic (PK) profiles in vitro improves prediction of in vivo efficacy in preclinical models
Authors: Singh Dharaminder , Deosarkar Sudhir P. , Cadogan Elaine , Flemington Vikki , Bray Alysha , Zhang Jingwen , Reiserer Ronald S. , Schaffer David K. , Gerken Gregory B. , Britt Clayton M. , Werner Erik M. , Gibbons Francis D. , Kostrzewski Tomasz , Chambers Christopher E. , Davies Emma J. , Montoya Antonio Ramos , Fok Jacqueline H. L. , Hughes David , Fabre Kristin , Wagoner Matthew P. , Wikswo John P. , Scott Clay W.
Published: May 2022

Test compounds used on in vitro model systems are conventionally delivered to cell culture wells as fixed concentration bolus doses; however, this poorly replicates the pharmacokinetic (PK) concentration changes seen in vivo and reduces the predictive value of the data. Herein, proof-of-concept experiments were performed using a novel microfluidic device, the Microformulator, which allows in vivo like PK profiles to be applied to cells cultured in microtiter plates and facilitates the investigation of the impact of PK on biological responses. We demonstrate the utility of the device in its ability to reproduce in vivo PK profiles of different oncology compounds over multiweek experiments, both as monotherapy and drug combinations, comparing the effects on tumour cell efficacy in vitro with efficacy seen in in vivo xenograft models. In the first example, an ERK1/2 inhibitor was tested using fixed bolus dosing and Microformulator-replicated PK profiles, in 2 cell lines with different in vivo sensitivities. The Microformulator-replicated PK profiles were able to discriminate between cell line sensitivities, unlike the conventional fixed bolus dosing. In a second study, murine in vivo PK profiles of multiple Poly(ADP-Ribose) Polymerase 1/2 (PARP) and DNA-dependent protein kinase (DNA-PK) inhibitor combinations were replicated in a FaDu cell line resulting in a reduction in cell growth in vitro with similar rank ordering to the in vivo xenograft model. Additional PK/efficacy insight into theoretical changes to drug exposure profiles was gained by using the Microformulator to expose FaDu cells to the DNA-PK inhibitor for different target coverage levels and periods of time. We demonstrate that the Microformulator enables incorporating PK exposures into cellular assays to improve in vitro–in vivo translation understanding for early therapeutic insight.
Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis
Authors: Zhou Hongli , Lu Yuting , Wei Hang , Chen Yixin , Limpanon Yanin , Dekumyoy Paron , Huang Ping , Shi Peiyao , Lv Zhiyue
Published: May 2022

Angiostrongylus cantonensis (AC) is well-documented that parasitizes the host brain and causes eosinophilic meningitis. The migration route of AC in permissive hosts is well demonstrated, while in nonpermissive hosts, it remains to be fully defined. In the present study, we exploited live imaging technology, morphological and pathological configuration analysis, and molecular biological technologies to explore the migration route of AC and the accompanying tissue damage in nonpermissive and permissive hosts. Our data indicated that, in nonpermissive host mouse, AC larvae migrated from intestinal wall to liver at 2 hours post-infection (hpi), from liver to lung at 4 hpi and then from lung to brain at 8 hpi. AC larval migration caused fatal lung injury (pneumonia) during acute and early infection phases, along with significant activation of Stat3/IL-6 signaling. In addition, AC induce sustained interstitial pneumonia in mouse and rat and pulmonary fibrosis only in rat during late infection phase. Moreover, during the early and late infection phases, Th2 cytokine expression and Stat3 and IL-6 signaling were persistently enhanced and myeloid macrophage cells were notably enriched in host lung, and administration of Stat3 and IL-6 inhibitors (C188-9 and LMT-28) attenuated AC infection-induced acute pneumonia in mice. Overall, we are the first to provide direct and systemic laboratory evidence of AC migration route in a nonpermissive host and report that infection with a high dose of AC larvae could result in acute and fatal pneumonia through Stat3/IL-6 signaling in mice. These findings may present a feasible to rational strategy to minimize the pathogenesis induced by AC.
Effect of cow’s milk with different PUFA n-6: n-3 ratios on performance, serum lipid profile, and blood parameters of grower gilts
Authors: Reis Leriana Garcia , Silva Thiago Henrique da , Salles Márcia Saladini Vieira , Andrade André Furugen Cesar , Martins Simone Maria Massami Kitamura , Takeuchi Paula Lumy , Vidal Ana Maria Centola , Netto Arlindo Saran
Published: May 2022

The concern with human health has increased the interest in producing foods enriched with polyunsaturated fatty acids (PUFA), directly or naturally, by inclusion in the animals’ diet. The positive effects such as antithrombotic, anti-inflammatory, and hypolipidemic have been observed in pigs and rats, used as human models for study. The present study evaluated the effect of cow’s milk with different lipid profiles on performance, serum fatty acid profile, biochemical analysis, and a complete blood count of gilts used as a human model. At 34 days, thirty gilts were equally distributed in three treatments. Experimental treatments were milk from cows without the oil supplementation (C), milk from cows fed an enriched diet with linseed oil (n-3), and milk from cows fed an enriched diet with soybean oil (n-6). Milk supplementation was performed until 190 days old, provided once in the morning. The n-3 and n-6 milk reduced the concentration of myristic acid in the blood and increased the leukocytes. Milk enriched with n-3 compared to n-6 reduced the stearic acid. In conclusion, milk with a better PUFA profile can reduce saturated fatty acids in the blood and alter the concentration of cells in the defense system.
MES-FPMIPv6: MIH-Enabled and enhanced secure Fast Proxy Mobile IPv6 handover protocol for 5G networks*^
Authors: Degefa Fikadu , Ryu Jihyeon , Kim Hyoungshick , Won Dongho
Published: May 2022

Fast Proxy Mobile IPv6 (FPMIPv6) is an extension of the PMIPv6 mobility management deployed as part of the next-generation internet protocol. It allows location-independent routing of IP datagrams, based on local mobility to IPv6 hosts without involvement of stations in the IP address signaling. A mobile node keeps its IP address constant as it moves from link to link, which avoids signaling overhead and latency associated with changing IP address. Even though local mobility requirements hold, it entails security threats such as Mobile Node, Mobile Access Gateway, as well as Local Mobility Anchor impersonation that go beyond those already exist in IPv6. As mobile station keeps moving across different serving networks, its IP remains constant during handover, and location privacy may not also be preserved. Moreover, homogeneous network dependence of PMIPv6 is one of the gaps, which FPMIPv6 could not mitigate. FPMIPv6 does not support heterogeneous network handover, for which numerous researchers have proposed Media Independent Handover (MIH) enabled FPMIPv6 schemes to allow fast handover among heterogeneous networks, but in the absence of security solutions. As a comprehensive solution, we propose a new handover authentication scheme and a key agreement protocol for the ‘MIH-enabled Network Only FPMIPv6’ model. As one of the basic requirements, mobility management should minimize signaling overhead, handover delay and power consumption of the mobile node. The proposed scheme improves wireless link overhead (mobile node overhead) by 6-86% as cell radius, wireless failure probability and number of hop vary. The security of the proposed scheme has also been analyzed under BAN logic and Automated Validation of Internet Security Protocols and Applications (AVISPA) tool and its performance has numerically been evaluated through a pre-determined performance matrix and found to be effective and preferably applicable compared with other schemes.
Reduced pro-inflammatory dendritic cell phenotypes are a potential indicator of successful peanut oral immunotherapy
Authors: Anvari Sara , Watkin Levi B. , Minard Charles G. , Schuster Kimberly , Hassan Oluwatomi , Anagnostou Aikaterini , Orange Jordan S. , Corry David B. , Davis Carla M.
Published: May 2022

Dendritic cells are important mediators in the early presentation of antigen and regulation of the differentiation of T cells. Peanut oral immunotherapy (POIT) results in desensitization in most peanut allergic individuals (responders), but not in others due to allergic reactions (non-responders). Delineation of early immunologic changes contributing to desensitization would help clarify the POIT mechanism of action. We analyzed dendritic cells in 15 pediatric subjects (5–12 years) undergoing a phase 1 single-center POIT study. We examined dendritic cells at baseline, 6-, 12-, 18- and 24-weeks after initiation of POIT and responders of therapy were compared to non-responders and healthy controls. The distribution frequency of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) from peripheral blood samples were measured in vitro. A general linear mixed model was used, and included fixed effects for cohort (responder, non-responder, or healthy control), time (0-, 6-, 12-, 18-, and 24-weeks), and the cohort-time interaction term. P-values were adjusted for multiple hypothesis testing using Tukey’s method. We observed that POIT responders had reduced TNFa producing myeloid dendritic cells (mDCs) compared to non-responders. Additionally, non-responders had increased OX40L expressing mDCs at 18-weeks compared to responders. In conclusion, our findings suggest that a reduced pro-inflammatory phenotype in DCs could potentially serve as a predictor of early outcome and success of POIT desensitization.
Geography and language divergence: The case of Andic languages
Authors: Koile Ezequiel , Chechuro Ilia , Moroz George , Daniel Michael
Published: May 2022

We study the correlation between phylogenetic and geographic distances for the languages of the Andic branch of the East Caucasian (Nakh-Daghestanian) language family. For several alternative phylogenies, we find that geographic distances correlate with linguistic divergence. Notably, qualitative classifications show a better fit with geography than cognacy-based phylogenies. We interpret this result as follows: The better fit may be due to implicit geographic bias in qualitative classifications. We conclude that approaches to classification other than those based on cognacy run a risk to implicitly include geography and geography-related factors as one basis of genealogical classifications.
The countercyclical long-term operating accrual-based trading strategy in the Stoxx Europe 600 index: The importance of asset and liability components
Authors: Sandoval Alberto , Márquez Javier , Cervera Ignacio
Published: May 2022

This work uses long-term operating accruals, rather than current, as an accounting measure to identify major anomalies. Past and abundant accounting and financial literature associates anomalies with problems of reliability and assigns lower reliability to long-term operating accruals than to current accruals. We investigate the relation between scaled operating accruals and size-adjusted abnormal returns for nonfinancial firms listed in the Stoxx Europe 600 index for the period 2000–2021. We find consistent evidence of (1) a higher long-term operating accrual anomaly than working capital accrual, especially, when asset and liability components are separated (2) long-short trading strategies aimed at taking advantage of the anomaly that achieves significant annual returns between 2% and 6% and (3) this trading strategy strongly reduces the risk of stock portfolios during an economic crisis due to its countercyclical nature. These findings have important implications not only for academics, but also for asset managers who want to protect the return of their stock portfolios from high market volatility.
Prevalence of and risk factors associated with HIV, Herpes Simplex Virus-type 2, Chlamydia trachomatis and Neisseria gonorrhoeae infections among 18–24 year old students attending Higher Learning Institutions in Mbeya-Tanzania
Authors: Mcharo Ruby Doryn , Kisinda Abisai , Njovu Lilian , Mcharo Miri , Mbwilo Florida , Mihale Getrude , Komba Beatrice , Andrew Ernest , Mayaud Philippe , Kroidl Arne , Ivanova Olena , Msuya Sia Emmanueli
Published: May 2022

Background

Sexually transmitted infections (STIs) are common among young people in low- and middle-income countries and are associated with negative reproductive and pregnancy outcomes. Most of the studies have assessed HIV among adolescents and young adults, with limited information on occurrence of other STIs in this population. This study aimed to describe the prevalence of and risk factors associated with Herpes Simplex Virus-type 2 (HSV-2), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Syphilis and HIV infection among young adults attending Higher Learning Institutions (HLIs) in Mbeya, Tanzania.

Methods

We conducted a cross-sectional study among students aged 18-24years attending HLIs in Mbeya-Tanzania, randomly selected using a computerized random number. Participants were tested for HSV-2, CT, NG, Syphilis and HIV infection. We used a self-administered questionnaire to collect information on sexual activity and risk factors to the tested STIs.

Results

We enrolled 504 students from 5 HLIs, with mean age of 21.5 years (SD 1.7). 17% of the students had at least one STI; prevalence was higher among females than males (21.1% versus 14.1%). CT (11%) and HSV-2 (6.1%) were the most common STIs, while NG (1.1%) and HIV (0.7%) infection had the least occurrence. None of the participants was diagnosed with Syphilis. In univariate analysis, predictors for STIs were Sex, inconsistent condom use in the past 4weeks, report of oral sex, sexual orientation (bisexual/homosexual) and having a sexual partner with an age-difference of at least 5years (either older or younger); while in the multivariate analysis, Sex, inconsistent condom use in the past 4weeks and sexual orientation (bisexual/homosexual) remained significant.

Conclusion

STIs such as Chlamydia and HSV-2 which are commonly asymptomatic are of concern among young adults attending HLIs. The latter is an important group that needs attention and recognition that is pivotal in transmission of STIs considering their risk. Information, Education and Communication (IEC) campaigns targeting young adults, especially those at HLIs, need to focus on exposure-risk minimization. Funding institutions that have invested heavily on HIV prevention campaigns should consider giving similar recognition to other STIs for a streamlined outcome.
Resistance training reduced luteinising hormone levels in postmenopausal women in a substudy of a randomised controlled clinical trial: A clue to how resistance training reduced vasomotor symptoms
Authors: Nilsson Sigrid , Henriksson Moa , Berin Emilia , Engblom David , Holm Anna-Clara Spetz , Hammar Mats
Published: May 2022

Background

Vasomotor symptoms (VMS) are common around menopause. Menopausal hormone therapy is the most effective treatment for VMS. Physical exercise has been proposed as an alternative treatment since physically active women have previously been found to experience fewer VMS than inactive women. In our randomised controlled trial on resistance training to treat VMS, sympoms were reduced by 50% in the intervention group compared with the control group.

Objectives

To propose a mechanism to explain how resistance training reduced VMS and to assess if luteinizing hormone (LH) and follicle stimulating hormone (FSH) were affected in accordance with the proposed mechanism.

Trial design and methods

A substudy of a randomized controlled trial on 65 postmenopausal women with VMS and low physical activity who were randomised to 15 weeks of resistance training three times per week (n = 33) or to a control group (n = 32). To be regarded compliant to the intervention we predecided a mean of two training sessions per week. The daily number of VMS were registered before and during the 15 weeks. Blood samples were drawn for analysis of LH and FSH at baseline and after 15 weeks.

Results

LH decreased significantly in the compliant intervention group compared with the control group (-4.0±10.6 versus 2.9±9.0, p = 0.028 with Mann-Whitney U test). FSH also decreased in the compliant intervention group compared with the control group, however not enough to reach statistical significance (-3.5±16.3 versus 3.2±18.2, p = 0.063 with Mann-Whitney U test). As previously published the number of hot flushes decreased significantly more in the intervention group than in the control group but there was no association between change in LH or FSH and in number of VMS.

Conclusions

We propose that endogenous opiods such as β-endorphin or dynorphin produced during resistance training decreased VMS by stimulating KNDγ-neurons to release neurokinin B to the hypothalamic thermoregulatory centre. Through effects on KNDγ-neurons, β-endorphin could also inhibit GnRH and thereby decrease the production of LH and FSH. The significanty decreased LH in the compliant intervention group compared with the control group was in accordance with the proposed mechanism.
Propagation laws of discontinuous gas supply in the excavation roadway
Authors: Gao Ke , Shi Lianzeng , Li Shengnan , Wen Liangxiu
Published: May 2022

An explosion with a discontinuous gas supply (DGS-explosion) is more complicated than a common secondary explosion. We present the results of a study on the propagation laws of the DGS-explosion induced by a gas explosion in excavation roadways. A rectangular tube was established using ANSYS, similar to an excavation roadway in an underground coal mine. The gas, flame, and shock wave propagation laws were determined by analyzing the explosive gas as it exited the excavation roadway. The results show that the initial explosion caused the flame generated in the DGS-explosion to be significantly stretched. Moreover, the shock wave was reflected by the end of the tube, which resulted in the reverse migration of the local gas after the DGS-explosion. Meanwhile, with the increase in local gas concentrations, the pressure peak and the entire explosion system can increase after the DGS-explosion. The flame region, temperature peak, and flame irregularity in the tube positively correlate with the concentration. These results can provide theoretical support and an experimental basis for preventing and responding to accidents caused by gas explosion accidents.
Long-term development of lens fluorescence in a twin cohort: Heritability and effects of age and lifestyle
Authors: Bjerager Jakob , Dabbah Sami , Belmouhand Mohamed , Kessel Line , Hougaard Jesper Leth , Rothenbuehler Simon P. , Sander Birgit , Larsen Michael
Published: May 2022

The blue-green autofluorescence of the ocular lens increases with age, glycemia and smoking, as the irreplaceable structural proteins of the lens slowly accumulate damage from the encounter with reactive molecular species. We have conducted a prospective study of lens autofluorescence over two decades in a twin cohort. The study included 131 phakic, non-diabetic adult twins (median age at follow-up 58 years, range 41–66 years) who were examined twice at an interval of 21 years. Change in anterior lens peak autofluorescence was analyzed in relation to age, current and baseline glycemia, cumulative smoking and heritability. The level of lens autofluorescence in the study population increased as a function of age and smoking (p ≤.002), but not as a function of glycemia (p ≥.069). Lens autofluorescence remained a highly heritable trait (90.6% at baseline and 93.3% at follow-up), but whereas the combined effect of age and cumulative smoking explained 57.2% of the variance in lens autofluorescence at baseline in mid-life, it only accounted for 31.6% at follow-up 21 years later. From mid to late adulthood, the level of blue-green fluorescence remained overwhelmingly heritable, but became less predictable from age, smoking habits and glycemic status. Presumably, as the lens ages, its intrinsic characteristics come to dominate over environmental and systemic factors, perhaps in a prelude to the development of cataract.
Circulating microRNA-122 in HCV cirrhotic patients with high frequency of genotype 3
Authors: Ullah Amin , Yu Xiaojie , Odenthal Margarete , Meemboor Sonja , Ahmad Bashir , Rehman Irshad ur , Ahmad Jamshaid , Ali Qurban , Nadeem Tariq
Published: May 2022

MicroRNA-122 (miR-122) is a liver abundant microRNA that is released upon liver injury. In the present study, we investigated the circulating miR-122 profiles in a Pakistani patients´ cohort with HCV chronic liver disease that was mainly based on HCV genotype 3 infections. From 222 patients with chronic HCV liver disease, classified as mild, moderate, or severe, serum samples were collected. Cell-free RNA was isolated and used for miR-122 quantification by qPCR. More than 60% of 222 patients were infected with HCV genotype 3. ALT values and HCV viral load showed no correlation with the HCV genotype. Circulating miR-122 levels were significantly upregulated in patients with cirrhosis. Notably, HCV patients with mild cirrhosis showed the most marked increase in serum miR-122 levels (p = 0.0001). Furthermore, we proved a positive correlation (r = 0.46) of miR-122 with the ALT values in patients with mild cirrhosis. Importantly, our data of increased miR-122 levels in serum samples obtained from a patient cohort with a high prevalence of chronic genotype 3 HCV infection confirmed the previous findings collected from cohorts with a high prevalence of genotype 1. Therefore, we suggest that miR-122 increase after HCV infection does not depend on the HCV genotype. In conclusion, our findings confirm that serum miR-122 levels are significantly upregulated in the HCV cirrhotic patients serving in particular as a biomarker for the non-advanced stages of cirrhosis, independently of the HCV genotype.
Reduced macular vessel density and inner retinal thickness correlate with the severity of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
Authors: Lin Chao-Wen , Yang Zih-Wei , Chen Chih-Hao , Cheng Yu-Wen , Tang Sung-Chun , Jeng Jiann-Shing
Published: May 2022

Background

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in NOTCH3, is the most common cause of hereditary cerebral small vessel disease. Whether it will involve systemic vasculopathy such as retinal vessel remains unknown. Optical coherence tomography angiography (OCT-A) is a noninvasive technique for visualising retinal blood flow. We analysed vessel density and retinal thickness in patients with CADASIL and investigated their correlations with disease severity.

Methods

This prospective study enrolled 35 patients with CADASIL (59 eyes) and 35 healthy controls (54 eyes). OCT-A was used to measure the vessel density of the macular region and the thickness of retinal layers. Patients with CADASIL were divided into stroke (n = 20) and nonstroke (n = 15) subgroups and underwent cognition and gait speed evaluation. Neuroimaging markers of cortical thickness, white matter hyperintensity, lacunae, and cerebral microbleeds were examined through brain magnetic resonance imaging.

Results

The OCT-A parameters, including vessel density, were comparable between the patients with CADASIL and the controls. In patients with CADASIL, vessel density in the superficial retinal plexus in the macula as was inner retinal thickness was significantly lower in the stroke than the nonstroke subgroup. Macular vessel density and inner retinal thickness were positively correlated with gait speed, while negatively correlated with number of lacunae.

Conclusions

OCT-A is potentially a useful tool for evaluating disease severity, ischaemic burden, and neurodegeneration in patients with advanced CADASIL.
Multi-system trajectories and the incidence of heart failure in the Framingham Offspring Study
Authors: Guardino Cara E. , Pan Stephanie , Vasan Ramachandran S. , Xanthakis Vanessa
Published: May 2022

Background

Heart failure is a multi-system disease, with non-cardiac systems playing a key role in disease pathogenesis.

Objective

Investigate whether longitudinal multi-system trajectories incrementally predict heart failure risk compared to single-occasion traits.

Methods

We evaluated 3,412 participants from the Framingham Heart Study Offspring cohort, free of heart failure, who attended examination cycle 5 and at least one examination between 1995–2008 (mean age 67 years, 54% women). We related trajectories for the following organ systems and metabolic functions to heart failure risk using Cox regression: kidney (estimated glomerular filtration rate), lung (forced vital capacity and the ratio of forced expiratory volume in one second/forced vital capacity), neuromotor (gait time), muscular (grip strength), cardiac (left ventricular mass index and heart rate), vascular function (pulse pressure), cholesterol (ratio of total/high-density lipoprotein), adiposity (body mass index), inflammation (C-reactive protein) and glucose homeostasis (hemoglobin A1c). Using traits selected via forward selection, we derived a trajectory risk score and related it to heart failure risk.

Results

We observed 276 heart failure events during a median follow up of 10 years. Participants with the ‘worst’ multi-system trajectory profile had the highest heart failure risk. A one-unit increase in the trajectory risk score was associated with a 2.72-fold increase in heart failure risk (95% CI 2.21–3.34; p<0.001). The mean c-statistics for models including the trajectory risk score and single-occasion traits were 0.87 (95% CI 0.83–0.91) and 0.83 (95% CI 0.80–0.86), respectively.

Conclusion

Incorporating multi-system trajectories reflective of the aging process may add incremental information to heart failure risk assessment when compared to using single-occasion traits.
Effect of early mobilization combined with early nutrition on acquired weakness in critically ill patients (EMAS): A dual-center, randomized controlled trial
Authors: Zhou Wendie , Yu Lili , Fan Yuying , Shi Baisheng , Wang Xiaohui , Chen Tianling , Yu Haixia , Liu Jie , Wang Xizhen , Liu Caihong , Zheng Huijia
Published: May 2022

Aim

The study aimed to investigate the effect of early mobilization combined with early nutrition (EMN) on intensive care unit-acquired weakness (ICU-AW) in intensive care unit (ICU) settings compared with early mobilization (EM) or routine care.

Methods

A prospective, dual-center, randomized controlled trial was conducted. The control group underwent standard care without a pre-established routine for mobilization and nutrition. The EM group underwent early, individualized, progressive mobilization within 24 h of ICU admission. The EMN group underwent early mobilization, similar to the EM group plus guideline-based early nutrition (within 48 h of ICU admission). The primary outcome was the occurrence of ICU-AW at discharge from the ICU. Secondary outcomes included muscle strength, functional independence, organ failure, nutritional status, duration of mechanical ventilation (MV), length of ICU stay, and ICU mortality at ICU discharge.

Results

A total of 150 patients were enrolled and equally distributed into the three groups. Patients undergoing routine care only were more susceptible to ICU-AW upon ICU discharge than those in the EM or EMN groups (16% vs. 2%; p = 0.014 for both), and had a lower Barthel Index than others (control vs. EM/EMN: 57.5 vs 70.0; p = 0.022). The EMN group had improved muscle strength (p = 0.028) and better nutritional status than the control group (p = 0.031). Both interventions were associated with a lower ICU-AW (EM vs. control: p = 0.027, OR [95% CI] = 0.066 [0.006–0.739]; EMN vs. control: p = 0.016, OR [95% CI] = 0.065 [0.007–0.607]).

Conclusion

EM and EMN had positive effects. There was little difference between the effects of EM and EMN, except for muscle strength improvement. Both EM and EMN may lead to a lower occurrence of ICU-AW and better functional independence than standard care. EMN might benefit nutritional status more than usual care and promote improvement in muscle strength.
Top-down effect of body representation on pain perception
Authors: Matsumuro Miki , Ma Ning , Miura Yuki , Shibata Fumihisa , Kimura Asako
Published: May 2022

Many studies on body representation intend to change the perceived size, material, and structure of the body. However, whether the perception of a stimulus can be modified by manipulating body representation remains largely unexplored. Thus, the current study investigated the relationship between transparency of body representation and pain perception. Using augmented reality technology, we made the participants’ limbs transparent and analyzed changes in body representation. Using a questionnaire, we confirmed that the participants perceived their limb as transparent. Simultaneously, their sense of ownership of the limb decreased, because they felt that it no longer belonged to their body. The participants were given an electrical stimulus to assess their subjective perception of pain intensity. An increase in limb opacity decreased the perception of pain, which, in turn, increased the feeling of transparency. These results suggested that the feeling of transparency in their limb favored the decrease in perceived pain. This effect was modified by body ownership, where high levels reinforced the analgesic effect. However, body ownership displayed a positive relationship with perceived pain. The study suggests that body transparency may constitute a strategy for decreasing refractory pain given that body ownership is retained at a high level.
Subtenon triamcinolone as an adjuvant in mitomycin-C-enhanced trabeculectomy in non-inflammatory glaucomas: A randomized clinical trial
Authors: Dias Diego T. , Almeida Izabela , Ushida Michele , Lopes Flavio S. , Kanadani Fábio N. , Gracitelli Carolina P. B. , Prata Tiago S.
Published: May 2022

This unicentric randomized clinical trial was designed to compare the surgical outcomes of mitomycin C-enhanced trabeculectomy (MMC-TRAB) with and without subtenon triamcinolone acetonide (TAAC) injection in patients with non-inflammatory glaucomas. This trial is registered at the Brazilian Registry of Clinical Trials (ReBEC) under the register number RBR-53f8nh. Consecutive non-inflammatory glaucoma patients requiring surgical intervention were randomized into two groups. In the control group, eyes underwent standard MMC-TRAB, while in the intervention group, besides the standard MMC-TRAB, these eyes also received a subtenon TAAC injection (4mg) close to the bleb site at the end of the surgery. The main outcomes of the study were surgical success rates, intraocular pressure (IOP) and number of medications at all timepoints. Success was defined as IOP ≤ 15 mmHg and subdivided in complete or qualified according to the need of medication. A total of 75 eyes of 63 different patients were included (intervention group = 39 eyes; control group = 36 eyes). There was no difference between groups at baseline (p>0.11). Multivariable regression analysis indicated that IOP levels were significantly lower in the intervention group at 18 and 24 months of follow-up when number of medications was considered as a covariate (P<0.001). Complete success rates were higher in the intervention group at 06 (90.9% vs 68.7%; p = 0.03), 12 (87.2% vs 66.7%; p = 0.02) and 18 months (87.2% vs 66.7%; p = 0.02). Additionally, although success rates at 24 months were higher in the intervention group (82.0% vs 66.7%; p = 0.09), this difference did not reach statistical significance. Qualified success rates did not significantly differ between groups at all timepoints. In conclusion, this study found significantly lower IOPs levels at 18 and 24 months of follow-up and higher complete success rates until 18 months of follow-up, with the use of subtenon TAAC as an adjuvant to standard MMC-TRABs in non-inflammatory glaucoma patients.
Glycemic control in newly insulin-initiated patients with type 2 diabetes mellitus: A retrospective follow-up study at a university hospital in Ethiopia
Authors: Sendekie Ashenafi Kibret , Teshale Achamyeleh Birhanu , Tefera Yonas Getaye
Published: May 2022

Background

Though many trials had examined the effectiveness of taking insulin with or without oral agents, there are limited real-world data, particularly among patients with type 2 diabetes mellitus (T2DM) in the resource limited settings. This study aimed to examine level of glycemic control among patients with T2DM after initiation of insulin and factors associated with poor glycemic control.

Methods

An analysis of retrospective medical records of patients with T2DM who initiated insulin due to uncontrolled hyperglycemia by oral agents was conducted from 2015–2020 in the University of Gondar Comprehensive Specialized Hospital. Difference in median fasting plasma glucose (FPG) before and after insulin initiations was examined by a Wilcoxon signed-rank test. Kruskal Wallis test was performed to explore difference in the median level of FPG among treatment groups. A logistic regression model was also used to identify associated factors of poor glycemic control after insulin initiation. Statistical significance was declared at p < 0.05.

Results

Of 424 enrolled patients with T2DM, 54.7% were males and the mean age was 59.3±9.3 years. A Wilcoxon signed-rank test showed that there was significant deference in FPG before and after insulin initiation (P < 0.001). A declining trend of blood glucose was observed during the 1-year follow-up period of post-initiation. However, majority of the participants did not achieve target glucose levels. Participants who had higher FPG and systolic blood pressure (SBP) before insulin initiation were found more likely to have poor glycemic control after insulin initiation. Similarly, patients who received atorvastatin compared with simvastatin were found to have poor glycemic control in the post-period of initiation (P = 0.04). Premixed insulin was associated with a lower likelihood of poor glycemic control than neutral protamine Hagedorn (NPH) insulin (P < 0.001).

Conclusion

Following insulin initiation, a significant change in glycemic level and declining trend of FPG was observed during a 1-year follow-up period. However, the majority of patients still had a poorly controlled glycemic level. Appropriate management focusing on predictors of glycemic control would be of a great benefit to achieve glycemic control.
Perspectives of homeless service providers on their work, their clients, and the healthcare system
Authors: Qian Cindy Wu , Hauser Joshua
Published: May 2022

Purpose

To describe the perspectives of homeless service providers who work for Chicago organizations that primarily serve persons experiencing homelessness.

Methods

A qualitative, cross-sectional study of Chicago homeless service providers (n = 17) consisting of a semi-structured interview and the Attitudes Toward the Homeless Inventory (ATHI). Interviews were analyzed for themes and patterns using inductive approach.

Results

Four categories of 16 themes describing homeless service providers’ perspectives and perceptions: 1) perspectives on work, 2) perspectives on the general population of those experiencing homelessness at large, 3) perceptions of the population of those experiencing homelessness based on client interactions, and 4) perceptions of hospitals and healthcare.

Conclusions

A richer understanding of the perspectives of homeless service may provide guidance in recruitment and training of workers in this area and offer insight into caring for persons experiencing homelessness in hospital settings.
Which hospital workers do (not) want the jab? Behavioral correlates of COVID-19 vaccine willingness among employees of Swiss hospitals
Authors: Asri Ankush , Asri Viola , Renerte Baiba , Föllmi-Heusi Franziska , Leuppi Joerg D. , Muser Juergen , Nüesch Reto , Schuler Dominik , Fischbacher Urs
Published: May 2022

In many countries, the current vaccination rates are stagnating, to the extent that vaccine hesitancy—the delay or refusal to take recommended vaccinations—forms a major obstacle to ending the COVID-19 pandemic. This tendency is particularly concerning when observed among healthcare workers who are opinion leaders on medical matters for their patients and peers. Our study surveys 965 employees of two large Swiss hospitals and profiles vaccine-hesitant hospital employees using not only socio-demographic characteristics, but also a comprehensive set of standard behavioral preference measures: (i) Big-5 personality traits, (ii) risk-, time- and social preferences, and (iii) perceived prevailing social norms. Using multinomial probit models and linear probability models, we find that vaccine-hesitant hospital employees are less patient and less likely to perceive vaccination as the prevailing social norm—in addition to replicating previously published socio-demographic results. Our findings are robust to a range of model specifications, as well as individual and situational covariates. Our study thus offers actionable policy implications for tailoring public-health communications to vaccine-hesitant hospital employees.
Evaluation of the economic characteristics of the fruit of 45 superior Camellia weiningensis Y.K. Li. trees
Authors: Yang Lu , Gao Chao , Wei Hongli , Long Li , Qiu Jie
Published: May 2022

Reports related to Camellia weiningensis Y.K. Li. are rare. We evaluated the economic characteristics of the mature fruit of 45 superior C. weiningensis trees using principal component analysis (PCA) and gray correlation analysis, and identified excellent germplasms according to performance. PCA was employed to reduce the dimensions. PCA was performed for the original 15 indices of fruit diameter, fruit length, fruit shape, single-fruit weight, pericarp thickness, oil yield, fresh seed rate, dry seed rate, dry kernel rate and palmitic acid, stearic acid, linolenic acid, oleic acid, linoleic acid and arachidonic acid contents. According to the requirements of a cumulative contribution rate ≥ 80% and an eigenvector value > 1, six principle components were selected. These indices underwent weighted summation to establish a function model for comprehensive evaluation. Finally, the comprehensive rankings of the cultivars according to PCA were compared with those according to gray correlation analysis. The genetic variation coefficients of the 15 parameters ranged from 2.24% (oleic acid content) to 22.70% (single-fruit weight, with a range of 21.34 g). The top ten excellent cultivars with the highest comprehensive scores according to PCA and those according to gray correlation analysis were compared. According to PCA, oleic acid content, fruit diameter, fruit length, pericarp thickness, arachidonic acid content and dry seed rate can serve as representative evaluation indicators of C. weiningensis. The outcomes obtained based on PCA were basically consistent with those obtained based on gray correlation analysis. Finally, nine excellent cultivars were finally determined, i.e., WY-1, WY-6, WY-8, WY-25, WY-27, WY-30, WY-33, WY-35, WY-38 and WY-44. The results obtained in terms of crown yield were basically consistent with the outcomes of the comprehensive assessments, which indicates the reliability of the assessment methods used in this study.
Integrated bioinformatics and statistical approaches to explore molecular biomarkers for breast cancer diagnosis, prognosis and therapies
Authors: Alam Md. Shahin , Sultana Adiba , Reza Md. Selim , Amanullah Md , Kabir Syed Rashel , Mollah Md. Nurul Haque
Published: May 2022

Integrated bioinformatics and statistical approaches are now playing the vital role in identifying potential molecular biomarkers more accurately in presence of huge number of alternatives for disease diagnosis, prognosis and therapies by reducing time and cost compared to the wet-lab based experimental procedures. Breast cancer (BC) is one of the leading causes of cancer related deaths for women worldwide. Several dry-lab and wet-lab based studies have identified different sets of molecular biomarkers for BC. But they did not compare their results to each other so much either computationally or experimentally. In this study, an attempt was made to propose a set of molecular biomarkers that might be more effective for BC diagnosis, prognosis and therapies, by using the integrated bioinformatics and statistical approaches. At first, we identified 190 differentially expressed genes (DEGs) between BC and control samples by using the statistical LIMMA approach. Then we identified 13 DEGs (AKR1C1,IRF9,OAS1,OAS3,SLCO2A1,NT5E,NQO1,ANGPT1,FN1,ATF6B,HPGD,BCL11A, andTP53INP1) as the key genes (KGs) by protein-protein interaction (PPI) network analysis. Then we investigated the pathogenetic processes of DEGs highlighting KGs by GO terms and KEGG pathway enrichment analysis. Moreover, we disclosed the transcriptional and post-transcriptional regulatory factors of KGs by their interaction network analysis with the transcription factors (TFs) and micro-RNAs. Both supervised and unsupervised learning’s including multivariate survival analysis results confirmed the strong prognostic power of the proposed KGs. Finally, we suggested KGs-guided computationally more effective seven candidate drugs (NVP-BHG712, Nilotinib, GSK2126458, YM201636, TG-02, CX-5461, AP-24534) compared to other published drugs by cross-validation with the state-of-the-art alternatives top-ranked independent receptor proteins. Thus, our findings might be played a vital role in breast cancer diagnosis, prognosis and therapies.
Risk assessment of atherosclerotic cardiovascular diseases before statin therapy initiation: Knowledge, attitude, and practice of physicians in Yemen
Authors: Al-Ashwal Fahmi Y. , Sulaiman Syed Azhar Syed , Sheikh Ghadzi Siti Maisharah , Kubas Mohammed Abdullah , Halboup Abdulsalam
Published: May 2022

Background

Risk evaluation of atherosclerotic cardiovascular disease (ASCVD) remains the cornerstone of primary prevention. The cardiovascular risk assessment can guide the decision-making on various preventive measures such as initiating or deferring statin therapy. Thus, our study aimed to assess the physicians’ knowledge, attitude, and practices regarding atherosclerotic cardiovascular diseases risk assessment. Also, we evaluated the physician-patient discussion and counseling practices before statin therapy initiation in concordance with recommendations from the latest clinical practice guideline.

Methods

A cross-sectional study was conducted between November 2020 and January 2021. A self-administered questionnaire was distributed to 350 physicians (GPs, residents, specialists, and consultants). Two trained pharmacists distributed the questionnaires in 5 major tertiary governmental hospitals and more than ten private hospitals. Also, private clinics were targeted so that we get a representative sample of physicians at different workplaces.

Results

A total of 270 physicians filled the questionnaire out of 350 physicians approached, with 14 being excluded due to high missing data, giving a final response rate of 73%. Participants had suboptimal knowledge and practices with a high positive attitude toward atherosclerotic cardiovascular diseases risk assessment. The knowledge and practices were higher among consultants, participants from the cardiology department, those with experience years of more than nine years, and those who reported following a specific guideline for cholesterol management or using a risk calculator in their practice. Notably, the risk assessment and counseling practices were lower among physicians who reported seeing more patients per day.

Conclusion

Physicians had overall low knowledge, suboptimal practices, and a high positive attitude toward cardiovascular risk assessment. Therefore, physicians’ training and continuing medical education regarding cholesterol management and primary prevention clinical practice guidelines are recommended. Also, the importance of adherence to clinical practice guidelines and their impact on clinical outcomes should be emphasized.
The longitudinal connection between depressive symptoms and inflammation: Mediation by sleep quality
Authors: Song Sunmi , DeMeo Natasha N. , Almeida David M. , Majd Marzieh , Engeland Christopher G. , Graham-Engeland Jennifer E.
Published: May 2022

Although there is a strong association between depressive symptoms and markers of inflammation, it remains unclear whether depressive symptoms at one point in life may predict inflammation later in life. Moreover, despite extant literature linking sleep with both depressive symptoms and inflammation, there is little research investigating poor sleep as a mechanism linking depressive symptoms with later inflammation. The links between depression and physical health can also vary by gender. In longitudinal analyses with data from the Midlife in the United States (MIDUS) study, we examined whether depressive symptoms were associated with inflammatory markers 11 years later and whether these associations were mediated by sleep disturbances or moderated by gender. Participants reported depressive symptoms and demographic information at baseline. At 11-year follow-up, the same participants (n = 968) reported depressive symptoms, sleep quality and duration using validated scale items, and provided a blood sample from which inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) were quantified. Actigraphy assessment of sleep was obtained in a subsample (n = 276). After adjusting for concurrent depressive symptoms and other relevant covariates, baseline depressive symptoms were associated with CRP 11 years later in the full sample, and with IL-6 among women. Subjective sleep quality mediated the association between depressive symptoms and CRP. Results suggest that depressive symptoms may be longitudinally associated with inflammation; however, directionality issues cannot be determined from the present work, particularly as inflammation markers (which might have been associated with baseline depressive symptoms) were not available at baseline. Findings further suggest that longitudinal associations between depressive symptoms and inflammation may potentially be explained by sleep and may reflect gender specific patterns.
Substance use disorder among adolescents before and during the COVID-19 pandemic in Uganda: Retrospective findings from a psychiatric ward registry
Authors: Kaggwa Mark Mohan , Abaatyo Joan , Alol Emmanuel , Muwanguzi Moses , Najjuka Sarah Maria , Favina Alain , Rukundo Godfrey Zari , Ashaba Scholastic , Mamun Mohammed A.
Published: May 2022

It has been reported that the COVID-19 pandemic has predisposed adolescents to risky behaviors such as substance use and subsequent substance use disorder (SUD). However, it is unknown how the pandemic has changed the prevalence of SUD among adolescents in Uganda. We aimed to determine the prevalence of SUD and associated factors among adolescents in southwestern Uganda. Retrospectively, psychiatry ward records from November 2018 to July 2021 were collected from the largest tertiary hospital in southwestern Uganda. A total of 441 adolescent records were included in the analysis, with a mean age was 17±1.88 years, and the majority were males (50.34%). The overall prevalence of SUD was 7.26% (5.90% and 9.80%beforeandduringthe pandemic). Despite a little rise in SUD (3.9% increment)duringthe COVID-19 pandemic, there was no statistical difference compared tobeforethe pandemic. The likelihood of being diagnosed with SUD was more among older adolescents at any period. In addition, having a diagnosis of bipolar mood disorder reduced the likelihood of SUDduringthe pandemic. This study indicated no statistical change in the diagnosis of SUD among adolescents before andduringthe COVID-19 pandemic. As older-male adolescents (17 to 19 years) were at higher risk of SUD, there is a need for early intervention for this group.