bluuebunny/crossref_metadata_2025 huggingface dataset:
DISTEMA: distance map-based estimation of single protein model accuracy with attentive 2D convolutional neural network
Authors: Chen Xiao , Cheng Jianlin
Published: April 2022

Background

Estimation of the accuracy (quality) of protein structural models is important for both prediction and use of protein structural models. Deep learning methods have been used to integrate protein structure features to predict the quality of protein models. Inter-residue distances are key information for predicting protein’s tertiary structures and therefore have good potentials to predict the quality of protein structural models. However, few methods have been developed to fully take advantage of predicted inter-residue distance maps to estimate the accuracy of a single protein structural model.

Result

We developed an attentive 2D convolutional neural network (CNN) with channel-wise attention to take only a raw difference map between the inter-residue distance map calculated from a single protein model and the distance map predicted from the protein sequence as input to predict the quality of the model. The network comprises multiple convolutional layers, batch normalization layers, dense layers, and Squeeze-and-Excitation blocks with attention to automatically extract features relevant to protein model quality from the raw input without using any expert-curated features. We evaluated DISTEMA’s capability of selecting the best models for CASP13 targets in terms of ranking loss of GDT-TS score. The ranking loss of DISTEMA is 0.079, lower than several state-of-the-art single-model quality assessment methods.

Conclusion

This work demonstrates that using raw inter-residue distance information with deep learning can predict the quality of protein structural models reasonably well. DISTEMA is freely athttps://github.com/jianlin-cheng/DISTEMA
Gene expression profiles provide insights into the survival strategies in deep-sea mussel (Bathymodiolus platifrons) of different developmental stages
Authors: Huang Junrou , Huang Peilin , Lu Jianguo , Wu Nengyou , Lin Genmei , Zhang Xilin , Cao Hong , Geng Wei , Zhai Bin , Xu Cuiling , Sun Zhilei
Published: April 2022

Background

Deep-sea mussels living in the cold seeps with enormous biomass act as the primary consumers. They are well adapted to the extreme environment where light is absent, and hydrogen sulfide, methane, and other hydrocarbon-rich fluid seepage occur. Despite previous studies on diversity, role, evolution, and symbiosis, the changing adaptation patterns during different developmental stages of the deep-sea mussels remain largely unknown.

Results

The deep-sea mussels (Bathymodiolus platifrons) of two developmental stages were collected from the cold seep during the ocean voyage. The gills, mantles, and adductor muscles of these mussels were used for the Illumina sequencing. A total of 135 Gb data were obtained, and subsequently, 46,376 unigenes were generated using de-novo assembly strategy. According to the gene expression analysis, amounts of genes were most actively expressed in the gills, especially genes involved in environmental information processing. Genes encoding Toll-like receptors and sulfate transporters were up-regulated in gills, indicating that the gill acts as both intermedium and protective screen in the deep-sea mussel. Lysosomal enzymes and solute carrier responsible for nutrients absorption were up-regulated in the older mussel, while genes related to toxin resistance and autophagy were up-regulated in the younger one, suggesting that the older mussel might be in a vigorous stage while the younger mussel was still paying efforts in survival and adaptation.

Conclusions

In general, our study suggested that the adaptation capacity might be formed gradually during the development of deep-sea mussels, in which the gill and the symbionts play essential roles.
The association between frailty and dignity in community-dwelling older people
Authors: Moradoghli Fereshteh , Darvishpoor Kakhki Ali , Esmaeili Roghayeh
Published: April 2022

Background

The population of people aged 60 and older is rapidly increasing in developing countries such as Iran due to declining birth rates and increased life expectancy. Old age is associated with increased risk for frailty and reduced dignity. Frailty is a clinical syndrome characterized by depletion of physical reserves and multiple system disorders, reducing the individual’s ability to cope with stressful events. Dignity is an inherent characteristic of human beings and respecting dignity is an ethical principle. This study investigated the association of frailty with dignity among older people in Tehran, Iran.

Methods

This correlational study was conducted on 200 individuals aged 60 years and older. Data collection relied on the Demographic Questionnaire, Frailty Index for Elders (FIFE) and the Patient Dignity Inventory (PDI). Data were analyzed with SPSS 25.

Results

The mean age of the participants was 68 ± 5.05 years; 62% of the participants were at risk for frailty, and 69% had few dignity-related problems. The multiple regression results showed that frailty was significantly associated with dignity (ß = 0.571, p < 0.001). The association was significant across all the dimensions of dignity measured by the PDI. The highest predictors of frailty included dependency (ß = 0.584, p < 0.001), followed by existential distress (ß = 0.560, p < 0.001), symptom distress (ß = 0.400, p = 0.400), social support (ß = 0.391, p < 0.001), and peace of mind (ß = 0.338, p < 0.001) in dignity.

Conclusions

The results show that higher levels of frailty in older people are associated with decreases in their dignity, and frailty was the leading predictor of dignity. Providers should develop programs to prevent and reduce frailty in those at risk and to enhance the dignity of the already frail.
A descriptive systematic review of the relationship between personality traits and quality of life of women with non-metastatic breast cancer
Authors: Wintraecken Veerle Marieke , Vulik Sophie , de Wild Sabine , Dirksen Carmen , Koppert Linetta B. , de Vries Jolanda , Smidt Marjolein L.
Published: April 2022

Background

Quality of life (QoL) is an important patient-reported outcome that has been studied extensively as an endpoint. There is a growing interest in factors that may influence QoL, such as personality. This descriptive systematic review examined the relationship between personality and QoL in women with non-metastatic breast cancer. 

Methods

On November 24th, 2020, with a update on March 7th, 2022, PubMed, PsycINFO, CINAHL, Web of Science and Embase were systematically searched for studies that assessed the direct relationship between personality traits and QoL among adult women diagnosed with non-metastatic breast cancer. The National Institutes of Health Study Quality Assessment Tool was used to assess the quality and risk of bias of the included studies. Three reviewers independently extracted data regarding objectives, population, setting, design, method, outcome measurements and key results. The results are descriptively reported.

Results

Twelve studies (6 cohort studies and 6 cross-sectional studies) were included. Three studies were rated as poor, one study was rated as good, and the remaining studies were rated as moderate. There was a small to moderate effect of personality on QoL as correlation coefficients ranged from 0.10 to 0.77, and the explained variance ranged from 4 to 43%. The (strength of the) relationship depended on the personality trait and QoL domain that was measured and was most apparent for the personality traits ‘optimism’ and ‘trait anxiety’ on psychosocial QoL domains. The results for the personality traits (unmitigated) agency, agreeableness, conscientiousness, novelty seeking, and self-efficacy indicated a smaller but statistically significant correlation between these personality traits and QoL.

Conclusions

The results confirm that personality affects QoL in women with non-metastatic breast cancer and thus provides evidence that personality traits are indeed important influential factors of QoL. It is therefore strongly recommended for all future QoL research to measure personality traits and use these variables as predictive factors, as they are needed to accurately interpret QoL. Information regarding personality traits provide physicians and patients with an interpretation of low or deterioration of QoL, which could guide physicians to improve their patients’ health outcomes and subsequently QoL using psycho-oncological support or treatment.
Safety and efficacy of 27-gauge transconjunctival vitrectomy for the diagnosis of posterior uveitis or pan uveitis of unknown origin
Authors: Sakai Atsushi , Tagami Mizuki , Misawa Norihiko , Yamamoto Manabu , Kohno Takeya , Honda Shigeru
Published: April 2022

Background

Diagnostic vitrectomy is an important method for evaluating uveitis, and its diagnostic utility is high regardless of whether the uveitis is infectious or non-infectious. The course of diagnostic vitreous surgery with 27-gauge pars plana vitrectomy and perioperative complications is reported.

Methods

An observational retrospective study of patients who underwent 27-gauge diagnostic vitrectomy due to atypical intraocular inflammation was conducted. The final diagnosis rate, complications due to surgery, preoperative visual acuity, and postoperative visual acuity (1 month and 6 months after surgery) were examined retrospectively.

Results

Diagnostic vitreous surgery was performed in 32 patients and 35 eyes (14 males and 18 females, age 14–85 years, median 67 years) during the study period. The average operation time was 52 min for 19 eyes with cataract surgery and 35 min for 16 eyes without cataract surgery. Preoperative log(minimum angle of resolution [MAR]) visual acuity was 0.84 ± 0.87, 1-month postoperative logMAR visual acuity was 0.41 ± 0.55 (p = 0.004, n = 28), and 6-month postoperative average logMAR visual acuity was 0.45 ± 0.73 (p = 0.012, n = 15). The diagnosis was made by diagnostic vitrectomy in 19 cases (54%). Postoperative complications were observed in 2 of 35 postoperative patients (5%); one involved increased intraocular pressure, and the other case involved vitreous hemorrhage of the eye, necessitating reoperation.

Conclusion

Diagnostic 27-gauge vitrectomy could be effective for evaluating intraocular inflammation.
Morphology characters of resected femoral and tibial surface in chinese population: intraoperative anthropometric study in patients at a tertiary hospital
Authors: Xu Yiming , Feng Bin , Dong Yulei , Zheng Zhibo , Bian Yanyan , Weng Xisheng
Published: April 2022

Backgrounds

Mismatch between knee surface and prosthesis components is related to postoperative complications. Morphological differences between ethnicity and gender may affect prosthesis coverage. The purpose of this study is to describe morphological characters of resected knee surface (distal femur, proximal tibia) in the Chinese population, analyze the influence of gender and other demographical factors, and validate the effect of ethnic difference by calculating the coverage of Western-designed knee prostheses on Chinese knee surface.

Methods

Intraoperative anthropometries were performed during total knee arthroplasty performed by one single team. After screening out severe deformities and bone defects, data were separated via prosthesis system. Multiple linear regression and partial correlation analysis of morphological parameters on age, gender, height, weight were used to find out independent factors influencing morphology. Based on the 5 mm-tolerance in the prosthesis, simulation on scatter plots was brought out to calculate the prosthesis coverage to the resected bone surface.

Results

A total of 865 cases of total knee arthroplasty were involved in this study. Though gender differences were found in all knee morphological parameters regardless of the type of prosthesis, significant association was only found between gender and mediolateral width of femoral surface after adjusting demographical factors (p < 0.001). The two included prosthesis systems, Genesis-II and Scorpio NRG covered most cases in at least one dimension. Males had lower complete coverage and higher no coverage rate on femurs. Asymmetry prostheses had higher lateral coverage on tibiae.

Conclusions

Based on our analysis, the only confirmed demographical factor in knee morphology is gender on femoral mediolateral length. Wider femoral prostheses for males may improve results of gender-specific prostheses. The overall fitness between Western-designed prostheses and Chinese knee surface is appliable, but the ratio of complete coverage is low. Further modification of prostheses systems can aim at the number of sizes and geometrical shapes.
Key drivers involved in the telemonitoring of covid-19 for self-health management: an exploratory factor analysis
Authors: Lo Presti Letizia , Testa Mario , Maggiore Giulio , Marino Vittoria
Published: April 2022

Background

The recent COVID-19 pandemic and the shortage of general practitioners has determined a strong pressure on the Italian health system. This critical issue highlighted the fundamental support of e-health services not only to lighten the workload of doctors, but also to offer patients a health service tailored to real needs. Therefore, the digital engagement platforms represent a valid aid, as they reconcile the efficiency needs of the healthcare system with the benefits for the patients involved. In this perspective, little is known about the main factors associated with use of telemonitoring platforms and their effectiveness. This paper investigates the critical success factors of telemonitoring platforms during COVID-19 in order to understand the mechanisms underlying patient participation with the health engagement platforms.

Methods

An exploratory factor analysis was used to explain the main dimensions of patient participation in the COVID-19 telemonitoring. A sample of 119 patients with a suspected or confirmed infection was used in the investigation. Moreover, an analysis of variance was calculated to identify the differences between three types of patients (infected, uninfected, with suspected infection) and verify the effectiveness of the platform.

Main Findings

There are six main factors underlying the use of the COVID-19 telemonitoring platform. “Self-Health Engagement” emerges as a novel factor. Moreover, compared to other platforms, cognitive engagement is a crucial trigger for effective telemonitoring.

Discussion

By identifying the main triggers involved in the use of health engagement platforms, we can improve the satisfaction of telemonitoring services for appropriate health-crisis management. Furthermore, the COVID-19 telemonitoring platform appears to improve health management for both patients and health care providers as it provides the patient with the necessary tools for Self-Health Management (SHM), as well as helping to enrich the literature on health care.

Conclusion

A new construct emerges in the study of digital telemonitoring platforms: “health self-engagement”, that is, an engagement based on self-care that demonstrates the decisive role assumed by both digital technology and patient participation in self-management.
Moniezia benedeni infection enhances neuromedin U (NMU) expression in sheep (Ovis aries) small intestine
Authors: Yao Wan-Ling , Liu Li-Ping , Wen Yan-Qiao , Wang Bao-Shan , Dong Jia-Qi , He Wan-Hong , Fan Xi-Ping , Wang Wen-Hui , Zhang Wang-Dong
Published: April 2022

Background

Neuromedin U (NMU) plays an important role in activating the group 2 innate lymphoid cells (ILC2s) and initiating the host’s anti-parasitic immune responses. It is aimed to explore the distribution characteristics of NMU in the sheep small intestine and the influence of Moniezia benedeni infection on them. In the present study, the pET-28a-NMU recombinant plasmids were constructed, and Escherichia coli. BL21 (DE3) were induced to express the recombinant protein. And then, the rabbit anti-sheep NMU polyclonal antibody was prepared and immunofluorescence staining was performed with it. The expression levels of NMU in the intestine of normal and Moniezia benedeni-infected sheep were detected by ELISA.

Results

The results showed that the molecular weight of the obtained NMU recombinant protein was consistent with the expected molecular (13 kDa) and it was expressed in the form of inclusion body. The titer and specificity of obtained rabbit anti-sheep NMU polyclonal antibody were good. The results of immunofluorescence analysis showed that the nerve fibers which specifically expressed NMU mainly extended from the ganglion in the submucosal to lamina propria (LP) in the sheep small intestine, and the expression level was relatively high; especially on the nerve fibers of LP around the intestinal glands. The expression levels were gradually increased from the duodenum to the ileum, and the levels in the jejunum and ileum were significantly higher than that in the duodenum (P < 0.05). In addition, scattered NMU positive cells were distributed in the epithelium of the jejunal crypts. Moniezia benedeni infection increased the expression of NMU in each intestinal segment, especially in the jejunum and ileum there were significant increase (P < 0.05).

Conclusions

It was suggested that Moniezia benedeni infection could be detected by the high expression of NMU in sheep enteric nervous, and which laid the foundation for further studies on whether NMU exerts anti-parasitic immunity by activating ILC2s. In addition, NMU was expressed in some intestinal gland epitheliums, which also provided a basis for studying its roles in regulation of the immune homeostasis. The present study laid the foundation for further revealing the molecular mechanism of sheep’s neural-immune interaction network perceiving the colacobiosis of parasites.
Biotechnological potential and initial characterization of two novel sesquiterpene synthases from Basidiomycota Coniophora puteana for heterologous production of δ-cadinol
Authors: Ringel Marion , Dimos Nicole , Himpich Stephanie , Haack Martina , Huber Claudia , Eisenreich Wolfgang , Schenk Gerhard , Loll Bernhard , Brück Thomas
Published: April 2022

Background

Terpene synthases are versatile catalysts in all domains of life, catalyzing the formation of an enormous variety of different terpenoid secondary metabolites. Due to their diverse bioactive properties, terpenoids are of great interest as innovative ingredients in pharmaceutical and cosmetic applications. Recent advances in genome sequencing have led to the discovery of numerous terpene synthases, in particular in Basidiomycota like the wood rotting fungus Coniophora puteana, which further enhances the scope for the manufacture of terpenes for industrial purposes.

Results

In this study we describe the identification of two novel (+)-δ-cadinol synthases from C. puteana, Copu5 and Copu9. The sesquiterpene (+)-δ-cadinol was previously shown to exhibit cytotoxic activity therefore having an application as possible, new, and sustainably sourced anti-tumor agent. In an Escherichia coli strain, optimized for sesquiterpene production, titers of 225 mg l−1 and 395 mg l−1, respectively, could be achieved. Remarkably, both enzymes share the same product profile thereby representing the first two terpene synthases from Basidiomycota with identical product profiles. We solved the crystal structure of Copu9 in its closed conformation, for the first time providing molecular details of sesquiterpene synthase from Basidiomycota. Based on the Copu9 structure, we conducted structure-based mutagenesis of amino acid residues lining the active site, thereby altering the product profile. Interestingly, the mutagenesis study also revealed that despite the conserved product profiles of Copu5 and Copu9 different conformational changes may accompany the catalytic cycle of the two enzymes. This observation suggests that the involvement of tertiary structure elements in the reaction mechanism(s) employed by terpene synthases may be more complex than commonly expected.

Conclusion

The presented product selectivity and titers of Copu5 and Copu9 may pave the way towards a sustainable, biotechnological production of the potentially new bioactive (+)-δ-cadinol. Furthermore, Copu5 and Copu9 may serve as model systems for further mechanistic studies of terpenoid catalysis.

Graphical Abstract
A cohort study evaluating the risk of stroke associated with long-term exposure to ambient fine particulate matter in Taiwan
Authors: Chen Pei-Chun , Sung Fung-Chang , Mou Chih-Hsin , Chen Chao W. , Tsai Shan P. , Hsieh Dennis H. P. , Hsu Chung Y.
Published: April 2022

Background

Evidences have shown that the stroke risk associated with long-term exposure to particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5) varies among people in North America, Europe and Asia, but studies in Asia rarely evaluated the association by stroke type. We examined whether long-term exposure to PM2.5 is associated with developing all strokes, ischemic stroke and hemorrhagic stroke.

Methods

The retrospective cohort study consisted of 1,362,284 adults identified from beneficiaries of a universal health insurance program in 2011. We obtained data on air pollutants and meteorological measurements from air quality monitoring stations across Taiwan in 2010–2015. Annual mean levels of all environmental measurements in residing areas were calculated and assigned to cohort members. We used Cox proportional hazards models to estimate hazard ratio (HR) and 95% confidence interval (CI) of developing stroke associated with 1-year mean levels of PM2.5 at baseline in 2010, and yearly mean levels from 2010 to 2015 as the time-varying exposure, adjusting for age, sex, income and urbanization level.

Results

During a median follow-up time of 6.0 years, 12,942 persons developed strokes, 9919 (76.6%) were ischemic. The adjusted HRs (95% CIs) per interquartile range increase in baseline 1-year mean PM2.5 were 1.03 (1.00–1.06) for all stroke, 1.06 (1.02–1.09) for ischemic stroke, and 0.95 (0.89–1.10) for hemorrhagic stroke. The concentration-response curves estimated in the models with and without additional adjustments for other environmental measurements showed a positively linear association between baseline 1-year mean PM2.5 and ischemic stroke at concentrations greater than 30 μg/m3, under which no evidence of association was observed. There was an indication of an inverse association between PM2.5 and hemorrhagic stroke, but the association no longer existed after controlling for nitrogen dioxide or ozone. We found similar shape of the concentration-response association in the Cox regression models with time-varying PM2.5 exposures.

Conclusion

Long-term exposure to PM2.5 might be associated with increased risk of developing ischemic stroke. The association with high PM2.5 concentrations remained significant after adjustment for other environmental factors.
Intracellular marriage of bicarbonate and Mn ions as “immune ion reactors” to regulate redox homeostasis and enhanced antitumor immune responses
Authors: Feng Yushuo , Liu Yaqing , Ma Xiaoqian , Xu Lihua , Ding Dandan , Chen Lei , Wang Zongzhang , Qin Ruixue , Sun Wenjing , Chen Hongmin
Published: April 2022

Background

Different from Fe ions in Fenton reaction, Mn ions can function both as catalyst for chemodynamic therapy and immune adjuvant for antitumor immune responses. In Mn-mediated Fenton-like reaction, bicarbonate ($${\text{HCO}}_{3}^{ - }$$

HCO

3

-

), as the most important component to amplify therapeutic effects, must be present, however, intracellular $${\text{HCO}}_{3}^{ - }$$

HCO

3

-

is strictly limited because of the tight control by live cells.

Results

Herein, Stimuli-responsive manganese carbonate-indocyanine green complexes (MnCO3-ICG) were designed for intracellular marriage of bicarbonate and Mn ions as “immune ion reactors” to regulate intracellular redox homeostasis and antitumor immune responses. Under the tumor acidic environment, the biodegradable complex can release “ion reactors” of Mn2+ and $${\text{HCO}}_{3}^{ - }$$

HCO

3

-

, and ICG in the cytoplasm. The suddenly increased $${\text{HCO}}_{3}^{ - }$$

HCO

3

-

in situ inside the cells regulate intracellular pH, and accelerate the generation of hydroxyl radicals for the oxidative stress damage of tumors cells because $${\text{HCO}}_{3}^{ - }$$

HCO

3

-

play a critical role to catalyze Mn-mediated Fenton-like reaction. Investigations in vitro and in vivo prove that the both CDT and phototherapy combined with Mn2+-enhanced immunotherapy effectively suppress tumor growth and realize complete tumor elimination.

Conclusions

The combination therapy strategy with the help of novel immune adjuvants would produce an enhanced immune response, and be used for the treatment of deep tumors in situ.
ACL reconstruction with femoral and tibial adjustable versus fixed-loop suspensory fixation: a retrospective cohort study
Authors: Schützenberger Sebastian , Keller F. , Grabner S. , Kontic D. , Schallmayer D. , Komjati M. , Fialka C.
Published: April 2022

Background

Cortical suspensory fixation (CSF) devices gain more and more popularity as a reliable alternative to interference screws for graft fixation in anterior cruciate ligament (ACL) reconstruction. Adjustable-loop fixation may be associated with increased anterior laxity and inferior clinical outcome. The purpose of the study was to compare anterior laxity and clinical outcome after minimally invasive all-inside ACL reconstruction using an adjustable-loop (AL) to a standard technique with a fixed-loop (FL) CSF device.

Methods

Patients who underwent primary single-bundle ACL reconstruction with a quadrupled hamstring autograft at a single institution between 2012 and 2016 were reviewed. In the AL group minimally invasive popliteal tendon harvesting was performed with an all-inside approach (femoral and tibial sockets). In the FL group a traditional anteromedial approach was used for tendon harvesting and a femoral socket and full tibial tunnel were drilled. An objective clinical assessment was performed with Telos x-rays and the International Knee Documentation Committee (IKDC) Objective Score. Patient-reported outcomes (PRO) included the IKDC Subjective Score, the Lysholm Knee Score, the Knee Injury and Osteoarthritis Score (KOOS) and the Tegner Activity Scale.

Results

A total of 67 patients were enrolled in this retrospective study with a mean follow-up of 4 (± 1.5) years. The groups were homogenous at baseline regarding age, gender, and the time to surgery. At follow-up, no statistically significant differences were found regarding anterior laxity (AL: 2.3 ± 3 mm vs. FL: 2.3 ± 2.6 mm, p = 0.981). PRO scores were comparable between the AL and FL groups (IKDC score, 84.8 vs. 88.8, p = 0.185; Lysholm 87.3 vs. 89.9, p = 0.380; KOOS 90.7 vs. 91.4, p = 0.720; Tegner 5.5 vs. 6.2, p = 0.085). The rate of saphenous nerve lesions was significantly lower in the AL group with popliteal harvesting of the tendon (8.3% vs. 35.5%, p = 0.014).

Conclusion

The use of an adjustable-loop device on the femoral and tibial side led to similar stability and clinical results compared to a fixed-loop device.
PTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development
Authors: Grinman Diego Y. , Boras-Granic Kata , Takyar Farzin M. , Dann Pamela , Hens Julie R. , Marmol Christina , Lee Jongwon , Choi Jungmin , Chodosh Lewis A. , Sola Martin E. Garcia , Wysolmerski John J.
Published: April 2022

Background

Parathyroid hormone-related protein (PTHrP) is required for embryonic breast development and has important functions during lactation, when it is produced by alveolar epithelial cells and secreted into the maternal circulation to mobilize skeletal calcium used for milk production. PTHrP is also produced by breast cancers, and GWAS studies suggest that it influences breast cancer risk. However, the exact functions of PTHrP in breast cancer biology remain unsettled.

Methods

We developed a tetracycline-regulated, MMTV (mouse mammary tumor virus)-driven model of PTHrP overexpression in mammary epithelial cells (Tet-PTHrP mice) and bred these mice with the MMTV-PyMT (polyoma middle tumor-antigen) breast cancer model to analyze the impact of PTHrP overexpression on normal mammary gland biology and in breast cancer progression.

Results

Overexpression of PTHrP in luminal epithelial cells caused alveolar hyperplasia and secretory differentiation of the mammary epithelium with milk production. This was accompanied by activation of Stat5 and increased expression of E74-like factor-5 (Elf5) as well as a delay in post-lactation involution. In MMTV-PyMT mice, overexpression of PTHrP (Tet-PTHrP;PyMT mice) shortened tumor latency and accelerated tumor growth, ultimately reducing overall survival. Tumors overproducing PTHrP also displayed increased expression of nuclear pSTAT5 and Elf5, increased expression of markers of secretory differentiation and milk constituents, and histologically resembled secretory carcinomas of the breast. Overexpression of PTHrP within cells isolated from tumors, but not PTHrP exogenously added to cell culture media, led to activation of STAT5 and milk protein gene expression. In addition, neither ablating the Type 1 PTH/PTHrP receptor (PTH1R) in epithelial cells nor treating Tet-PTHrP;PyMT mice with an anti-PTH1R antibody prevented secretory differentiation or altered tumor latency. These data suggest that PTHrP acts in a cell-autonomous, intracrine manner. Finally, expression of PTHrP in human breast cancers is associated with expression of genes involved in milk production and STAT5 signaling.

Conclusions

Our study suggests that PTHrP promotes pathways leading to secretory differentiation and proliferation in both normal mammary epithelial cells and in breast tumor cells.
Preventing disease progression in multiple sclerosis—insights from large real-world cohorts
Authors: Engel Sinah , Zipp Frauke
Published: April 2022

Multiple sclerosis is a chronic neuroinflammatory disease with a highly heterogeneous disease course. Preventing lasting disability requires early identification of persons at risk and novel approaches towards patient stratification for personalized treatment decisions. In this comment, we discuss the importance of large datasets of real-world cohorts in order to address this unmet need.
A prospective investigation into the association between the gut microbiome composition and cognitive performance among healthy young adults
Authors: Oluwagbemigun Kolade , Schnermann Maike E. , Schmid Matthias , Cryan John F. , Nöthlings Ute
Published: April 2022

Background

There is emerging evidence that the gut microbiome composition is associated with several human health outcomes, which include cognitive performance. However, only a few prospective epidemiological studies exist and none among young adults. Here we address the gap in the literature by investigating whether the gut microbiome composition is prospectively linked to fluid intelligence among healthy young adults.

Methods

Forty individuals (65% females, 26 years) from the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study provided a fecal sample for gut microbiome composition and subsequently (average of 166 days) completed a cognitive functioning test using the Cattell’s Culture Fair Intelligence Test, revised German version (CFT 20-R). The assessment of the gut microbiome at the genera level was by 16S rRNA V3-V4 Illumina sequencing. The relative abundance of 158 genera was summarized into bacterial communities using a novel data-driven dimension reduction, amalgamation. The fluid intelligence score was regressed on the relative abundance of the bacterial communities and adjusted for selected covariates.

Results

The 158 genera were amalgamated into 12 amalgams (bacterial communities), which were composed of 18, 6, 10, 14, 8, 10, 16, 13, 12, 12, 3, and 11 genera. Only the 14-genera bacterial community, named the “Ruminococcaceae- and Coriobacteriaceae-dominant community” was positively associated with fluid intelligence score (β = 7.8; 95% CI: 0.62, 15.65,P = 0.04).

Conclusion

Among healthy young adults, the abundance of a gut bacterial community was associated with fluid intelligence score. This study suggests that cognitive performance may potentially benefit from gut microbiome-based intervention.
Characterization of transposable elements within the Bemisia tabaci species complex
Authors: Sicat Juan Paolo A. , Visendi Paul , Sewe Steven O. , Bouvaine Sophie , Seal Susan E.
Published: April 2022

Background

Whiteflies are agricultural pests that cause negative impacts globally to crop yields resulting at times in severe economic losses and food insecurity. The Bemisia tabaci whitefly species complex is the most damaging in terms of its broad crop host range and its ability to serve as vector for over 400 plant viruses. Genomes of whiteflies belonging to this species complex have provided valuable genomic data; however, transposable elements (TEs) within these genomes remain unexplored. This study provides the first accurate characterization of TE content within the B. tabaci species complex.

Results

This study identified that an average of 40.61% of the genomes of three whitefly species (MEAM1, MEDQ, and SSA-ECA) consists of TEs. The majority of the TEs identified were DNA transposons (22.85% average) while SINEs (0.14% average) were the least represented. This study also compared the TE content of the three whitefly genomes with three other hemipteran genomes and found significantly more DNA transposons and less LINEs in the whitefly genomes. A total of 63 TE superfamilies were identified to be present across the three whitefly species (39 DNA transposons, six LTR, 16 LINE, and two SINE). The sequences of the identified TEs were clustered which generated 5766 TE clusters. A total of 2707 clusters were identified as uniquely found within the whitefly genomes while none of the generated clusters were from both whitefly and non-whitefly TE sequences.

This study is the first to characterize TEs found within different B. tabaci species and has created a standardized annotation workflow that could be used to analyze future whitefly genomes.

Conclusion

This study is the first to characterize the landscape of TEs within the B. tabaci whitefly species complex. The characterization of these elements within the three whitefly genomes shows that TEs occupy significant portions of B. tabaci genomes, with DNA transposons representing the vast majority. This study also identified TE superfamilies and clusters of TE sequences of potential interest, providing essential information, and a framework for future TE studies within this species complex.
Psychological predictors of insomnia, anxiety and depression in university students: potential prevention targets
Authors: Lindsay Julia A. B. , McGowan Niall M. , King Nathan , Rivera Daniel , Li Melanie , Byun Jin , Cunningham Simone , Saunders Kate E. A. , Duffy Anne
Published: April 2022

Background

Perfectionism, low self-esteem and external locus of control are psychological constructs linked to insomnia, anxiety and depression. Examining how these constructs impact mental health and serve as risk factors for the development of clinically significant symptoms may help direct psychological support resources and preventative measures for university students.

Aims

To longitudinally examine associations between the aforementioned psychological constructs and symptoms of insomnia, anxiety and depression in a large representative sample of first-year university students.

Method

Electronic surveys including validated measures of the predictors and outcomes were emailed to all first-year undergraduate students at entry to a major Canadian university, and followed up on at conclusion of the academic year.

Results

Compared with healthy sleepers, students screening positive for insomnia had lower self-esteem, higher self-evaluative perfectionism and increased external locus of control (allP< 0.001). Self-evaluative perfectionism (standardisedβ= 0.13,P< 0.01), self-esteem (β= −0.30,P< 0.001) and external locus of control (β= 0.07,P= 0.02) measured at entry were significantly associated with insomnia symptoms at follow-up. Insomnia symptoms at entry were strong predictors of symptoms of depression (β= 0.15,P< 0.001) and anxiety (β= 0.16,P< 0.001) at follow-up, even after controlling for baseline symptoms of those disorders.

Conclusions

Perfectionism, low self-esteem and external locus of control may predispose the development of insomnia symptoms in university students. In turn, insomnia symptoms appear to be robust predictors for depressive and anxiety symptoms. Sleep may be an important prevention target in university students.
The Price of Inequality in Type 1 Diabetes Management
Authors: Herringshaw Emilee
Published: April 2022

The purpose of this paper is to examine the compounded disparities in diabetes management and how disease burden is amplified by socioeconomic conditions. Access to tools that equip care is explored in relation to income, education, race, and insurance coverage. Commentary is also provided from the perspective of a patient who has managed diabetes for 25 years and is currently a third-year medical student. From this experience, she understands firsthand the demand and complexity of disease management. Through her observations in the hospital, she also identifies how disparities shape care for individuals managing this challenging disease. Lower socioeconomic status, education level, non-White race, and noncommercial insurance are among variables that restrict access to technology. The various influences that shape technological access in combination with the observations from a patient managing T1D serve to demonstrate the multifactorial challenges encompassed in care acquisition.
Interactions of cytosolic tails in the Jen1 carboxylate transporter are critical for trafficking and transport activity
Authors: Barata-Antunes Cláudia , Talaia Gabriel , Broutzakis George , Ribas David , De Beule Pieter , Casal Margarida , Stefan Christopher J. , Diallinas George , Paiva Sandra
Published: April 2022

Plasma membrane (PM) transporters of the major facilitator superfamily (MFS) are essential for cell metabolism, growth and response to stress or drugs. In Saccharomyces cerevisiae, Jen1 is a monocarboxylate/H+ symporter that provides a model to dissect the molecular details underlying cellular expression, transport mechanism and turnover of MFS transporters. Here, we present evidence revealing novel roles of the cytosolic N- and C-termini of Jen1 in its biogenesis, PM stability and transport activity, using functional analyses of Jen1 truncations and chimeric constructs with UapA, an endocytosis-insensitive transporter of Aspergillus nidulans. Our results show that both N- and C-termini are critical for Jen1 trafficking to the PM, transport activity and endocytosis. Importantly, we provide evidence that Jen1 N- and C-termini undergo transport-dependent dynamic intramolecular interactions, which affect the transport activity and turnover of Jen1. Our results support an emerging concept where the cytoplasmic termini of PM transporters control transporter cell surface stability and function through flexible intramolecular interactions with each other. These findings might be extended to other MFS members to understand conserved and evolving mechanisms underlying transporter structure–function relationships.

This article has an associated First Person interview with the first authors of the paper.
Protocol for a Longitudinal Study of the Determinants of Metabolic Syndrome Risk in Young Adults
Authors: Pomeroy Alexander , Bates Lauren C. , Stoner Lee , Weaver Mark A. , Moore Justin B. , Nepocatych Svetlana , Higgins Simon
Published: April 2022

Context

As many as 76.7% of U.S. young adults have at least one metabolic syndrome risk factor. Often undetected, metabolic syndrome risk factors cluster with other risk factors increasing risk of future cardiometabolic disease. The prevention of metabolic syndrome risk accrual through early behavioral interventions is crucial for at-risk populations.

Objectives

This article outlines the protocol for the Health E Start study, including objectives, methodology, ethics, and dissemination. Additionally, we discuss the goals of the National Institutes of Health Research Enhancement Award (R15) that funded this project and how this funding will facilitate the comprehensive training of undergraduate researchers. The long-term goal of the study is to develop a theoretically driven intervention for the prevention of metabolic syndrome risk development in college students. To facilitate this goal, the aims are to identify 1) the behavioral targets for the prevention of metabolic syndrome risk development and 2) the motivations behind such behaviors to develop a theoretical framework for use in intervention design.

Design

This is a longitudinal observational design setting.

Setting

This study focuses on the transition from living at home to independent living at colleges across the United States.

Participants

The participants of this study are high school seniors (n = 150) who will be transitioning to college within 3 months of graduating.

Main Outcome Measure

For aim 1, metabolic syndrome risk will be quantified into a risk score using a principal components analysis of traditional risk factors. Associations between changes in lifestyle behaviors and changes in the risk score will identify population-specific behavioral targets. For aim 2, changes in psychological, social, and environmental antecedents of observed behaviors will be identified.

Conclusions

Identifying the relationship between behavior change and metabolic syndrome risk and the psychosocial and environmental predictors of observed behavior changes will facilitate the design of targeted interventions for the prevention of metabolic syndrome risk progression in the early college years.
Sea grapes powder with the addition of tempe rich in collagen: An anti-aging functional food
Authors: Permatasari Happy Kurnia , Nurkolis Fahrul , Vivo Christopherous Diva , Noor Sutamara Lasurdi , Rahmawati Rahmawati , Radu Son , Hardinsyah Hardinsyah , Taslim Nurpudji Astuti , Mayulu Nelly , Wewengkang Defny Silvia , Kuswari Mury , Batubara Siti Chairiyah , Gunawan William Ben , Nahdi Maizer Said
Published: April 2022

Background: This study aimed to determine the potential anti-aging effects of sea grapes and tempe (fermented soybeans) collagen particle size, by measuring the activities of anti-glycation, antioxidant, and tyrosinase inhibitors. Methods: Collagen was isolated from freeze-dried sea grapes and tempe powder and treated with different NaOH concentrations (0.10 M; 0.20 M; 0.30 M), and CH3COOH 1 M solution, separately. The collagen particle size was adjusted by stirring at 1000 rpm for 5 and 10 hours. 2,2-diphenyl-1-picrylhydrazyl (DPPH) was used to measure the antioxidant activity, and L-tyrosine and L-DOPA (l-3,4-dihydroxyphenylalanine) was used as a marker of tyrosine inhibition. Results:  The collagen treated with 0.10 M NaOH produced the highest collagen yield (11.65%), and the largest particle size (2455 nm). Additionally, this collagen, when treated for 5 hours, exhibited 24.70% antioxidant activity, 62.60% anti-glycation, 8.97% L-tyrosine, and 26.77% L-Dopa inhibition activities. Meanwhile, the collagen treated for 10 hours had a 9.98% antioxidant activity, 41.48% anti-glycation, 7.89% L-tyrosine, and 2.67% L-Dopa inhibition activity. Conclusion: Sea grapes and tempe collagen powder treated with 0.10 M NaOH and stirred for 5 hours, possess the best potential anti-aging properties as a functional food.
Recognising the deterioration of patients in acute care wards: a qualitative study
Authors: Beane Abi , Wijesiriwardana Wageesha , Pell Christopher , Dullewe N. P. , Sujeewa J. A. , Rathnayake R. M. Dhanapala , Jayasinghe Saroj , Dondorp Arjen M. , Schultsz Constance , Haniffa Rashan
Published: April 2022

Background: Infrastructure, equipment and staff constraints are often cited as barriers to the recognition and rescue of deteriorating patients in resource-limited settings. The impact of health-system organisation, decision-making and organisational culture on recognition of deterioration is however poorly understood. This study explores how health care providers recognise deterioration of patients in acute care in Sri Lanka.

Methods: In-depth interviews exploring decision making and care processes related to recognition of deterioration, were conducted with a purposive sample of 23 health care workers recruited from ten wards at a district hospital in Sri Lanka. Interviews were audio-recorded, transcribed and coded thematically, line-by-line, using a general inductive approach.

Results: A legacy of initial assessment on admission and inimical organisational culture undermined recognition of deteriorating patients in hospital. Informal triaging at the time of ward admission resulted in patients presenting with red-flag diagnoses and vital sign derangement requiring resuscitation being categorised as "bad". The legacy of this categorisation was a series of decision-making biases anchored in the initial assessment, which remained with the patient throughout their stay. Management for patients categorised as “bad” was prioritised by healthcare workers coupled with a sense of fatalism regarding adverse outcomes. Health care workers were reluctant to deviate from the original plan of care despite changes in patient condition (continuation bias). Organisational culture - vertical hierarchy, siloed working and a reluctance to accept responsibility- resulted in omissions which undermined recognition of deterioration. Fear of blame was a barrier to learning from adverse events.

Conclusions: The legacy of admission assessment and hospital organisational culture undermined recognition of deterioration. Opportunities for improving recognition of deterioration in this setting may include establishing formal triage and medical emergency teams to facilitate timely recognition and escalation.
Słowacki apokryficzny? Twórcza lektura Biblii w wykonaniu przemienionego poety a status materii w myśli genezyjskiej
Authors: Rzepniewska-Kosińska Anna
Published: April 2022

Artykuł pokazuje sposób, w jaki Juliusz Słowackiego czytał Biblię w latach czterdziestych XIX wieku, czyli po przemianie zwanej mistyczną. Choć to zagadnienie ma długą tradycję badawczą, wciąż pewne jego wątki domagają się interpretacji. Na odczytywaniu twórczości z tych lat ciąży bowiem postrzeganie poety jako „Słowackiego od duchów” – skupionego wyłącznie na sferze duchowej, a tym samym deprecjonującego materialną warstwę istnienia. W istocie romantyk nie neguje cielesności, za to poddaje ją refleksji, a uzasadnienia jej statusu poszukuje właśnie w Biblii – przede wszystkim w pierwszych rozdziałach Księgi Rodzaju. Odczytanie Słowackiego odbiega od oryginału w kilku aspektach, co pozwala sądzić, że nie zajmuje się on hermeneutyką Pisma Świętego, lecz dąży do dopełnienia biblijnego przekazu z perspektywy własnego objawienia. Interpretacja tych przesunięć (zawartych w tzw. Dziele filozoficznym) pozwala dostrzec u poety dążenie do konkretyzacji wizji biblijnej oraz zainteresowanie materialną rzeczywistością pierwszych dni świata. Pokazuje Słowackiego jako wieloletniego, czujnego czytelnika Biblii, próbującego doprecyzować jej treść, jak również myśliciela – twórcę myśli genezyjskiej – ceniącego materię bardziej, niż zwykło się przyjmować.