bluuebunny/crossref_metadata_2025 huggingface dataset:
GCMM: graph convolution network based on multimodal attention mechanism for drug repurposing
Authors: Zhang Fan , Hu Wei , Liu Yirong
Published: September 2022

Background

The main focus of in silico drug repurposing, which is a promising area for using artificial intelligence in drug discovery, is the prediction of drug–disease relationships. Although many computational models have been proposed recently, it is still difficult to reliably predict drug–disease associations from a variety of sources of data.

Results

In order to identify potential drug–disease associations, this paper introduces a novel end-to-end model called Graph convolution network based on a multimodal attention mechanism (GCMM). In particular, GCMM incorporates known drug–disease relations, drug–drug chemical similarity, drug–drug therapeutic similarity, disease–disease semantic similarity, and disease–disease target-based similarity into a heterogeneous network. A Graph Convolution Network encoder is used to learn how diseases and drugs are embedded in various perspectives. Additionally, GCMM can enhance performance by applying a multimodal attention layer to assign various levels of value to various features and the inputting of multi-source information.

Conclusion

5 fold cross-validation evaluations show that the GCMM outperforms four recently proposed deep-learning models on the majority of the criteria. It shows that GCMM can predict drug–disease relationships reliably and suggests improvement in the desired metrics. Hyper-parameter analysis and exploratory ablation experiments are also provided to demonstrate the necessity of each module of the model and the highest possible level of prediction performance. Additionally, a case study on Alzheimer’s disease (AD). Four of the five medications indicated by GCMM to have the highest potential correlation coefficient with AD have been demonstrated through literature or experimental research, demonstrating the viability of GCMM. All of these results imply that GCMM can provide a strong and effective tool for drug development and repositioning.
Sexual selection leads to positive allometry but not sexual dimorphism in the expression of horn shape in the blue wildebeest, Connochaetes taurinus
Authors: Gerstenhaber Chloé , Knapp Andrew
Published: September 2022

Sexual selection is thought to be an important driver of adaptation, speciation and extinction. Empirically testing these predictions across macroevolutionary timescales first requires an understanding of the morphology of secondary sexual traits in extant taxa. We used three-dimensional geometric morphometrics to analyse a large sample of the skull of the blue wildebeest, Connochaetes taurinus, in which horns are found in both sexes but only used in intrasexual competition in males. We show that the horns fit several predictions of secondary sexual traits; overall skull shape is significantly correlated with size (R2 = 0.38, p = 0.001), and the sexually selected horns show drastically higher growth rates and variation than any other skull element, supporting previous findings. We also find that despite showing significant sexual dimorphism in shape and size (R2 = 0.21, p = 0.001), allometric growth trajectories of sexes are identical (R2 = 0.01, p = 0.635) and dimorphism is not readily detectable without prior knowledge of sex, and is not possible when shape is corrected for size. Our results show that even with strong sexual selection operating in only one sex, the expression of secondary sexual traits may show characteristic and indistinguishable patterns of growth and variance in both sexes.
Outcome of anticoagulation with rivaroxaban in patients with non-retrieved inferior vena cava filters for the prevention of filter thrombosis: a retrospective cohort study
Authors: Wang Baoyan , Jiang Chenxiao , Zhang Yepeng , Li Xiaoqiang , Xu Hang
Published: September 2022

Background

Non-retrieved inferior vena cava filter (IVCF) is associated with some severe complications, such as filter thrombosis. The aim of this retrospective cohort study was to evaluate the outcome of rivaroxaban for the prevention of filter thrombosis in patients with non-retrieved IVCF.

Methods

The study based on the VTE registry databases was limited to patients with non-retrieved IVCF treated at Nanjing Drum Tower Hospital from January 2012 to December 2017. Outcomes included filter thrombosis, total bleeding events, death.

Results

A total of 202 patients were enrolled in the study and divided into rivaroxaban group and warfarin group. Mean follow-up period of the two groups was 57.4 ± 20.8 and 62.2 ± 23.0 months, respectively. In risk factors for VTE, transient factors (P = 0.008) and history of VTE (P = 0.028) were statistically different between the two groups. A total of 13 (6.4%) patients developed filter complications, of which 4 (3.5%) and 5 (5.7%) patients in rivaroxaban group and warfarin group developed filter thrombosis, respectively, without significant difference (P = 0.690). The total bleeding events in rivaroxaban group, including major bleeding and clinically relevant and non-major (CRNM) bleeding, were significantly lower than that in warfarin group (P = 0.005). Adjusting for hypertension, transient risk factors, history of VTE and cancer, no differences in the hazard ratio for outcomes were notable.

Conclusions

It is necessary to perform a concomitant anticoagulation in patients with non-retrieved filters. Rivaroxaban can be an alternative anticoagulant option for the prevention of filter thrombosis.
Cone-beam computed tomography-based analysis of maxillary sinus pneumatization extended into the alveolar process in different age groups
Authors: Wu Xingsheng , Cai Qiudong , Huang Di , Xiong Peiwen , Shi Lianshui
Published: September 2022

Objective

This study aimed to measure the amount of maxillary sinus pneumatization (MSP) extended into alveolar processes in different age groups via cone-beam computed tomography (CBCT) and its association with age.

Methods

The data of 293 adult patients (533 maxillary sinuses) who underwent CBCT at our hospital from January 2020 to October 2020 were analyzed and divided into the following age groups: group I (18–34 years old, youth group), group II (35–59 years old, middle-aged group) and group III (≥ 60 years old, elderly group). The distance between the lowest point of the maxillary sinus floor and nasal cavity floor in the central area of the maxillary posterior teeth was measured and recorded as the amount of MSP. Further, according to the positional relation between the maxillary posterior teeth and maxillary sinus floor, MSP was divided into type I (normal pneumatization) and type II (extensive pneumatization). The distribution of pneumatization types and degree and change of pneumatization for the different age groups were also analyzed. P < 0.05 was used as the threshold for statistical significance.

Results

The amount of MSP of group I [(3.75 ± 3.77) mm] was significantly higher than that of group II [(2.30 ± 4.48) mm] and group III [(2.09 ± 4.70) mm], but there was no significant difference between group II and group III. We also found that the amount decreased gradually with increasing age (rs = − 0.2), with the youth group showing a higher prevalence of extensive pneumatization (youth vs. middle-age vs. elderly: 66.44% vs. 36.81% vs. 22.28%, respectively). There was no statistically significant difference in the amount of MSP between males and females and between left and right maxillary sinus in each group (P > 0.05).

Conclusion

The amount of MSP was significantly higher in the 18–34 years old group compared to older age groups, showed a decreasing trend with age and was not associated with sex and maxillary sinus sides.
Juvenile diabetes and systemic sclerosis: just a coincidence?
Authors: Mastrangelo Greta , Meneghel Alessandra , Martini Giorgia , Moretti Carlo , Zulian Francesco
Published: September 2022

Background

Limited joint mobility (LJM), previously known as cheiroarthropathy, refers to the presence of reduced extension at the finger joints in people with diabetes and may be associated with scleroderma-like syndromes such as diabetic sclerodactyly.

While scleroderma-like syndromes and LJM have been observed in patients with long-term diabetes and associated complications, the coexistence of diabetes with Juvenile systemic sclerosis (jSSc) is rarely described.

Case presentation

We describe the case of a 14-year-old boy with long-lasting type 1 diabetes (T1D) and suspected LJM associated with Raynaud phenomenon, sclerodactyly and tapering of the fingertips. A comprehensive work-up showed positive autoantibodies (ANA, anti-Ro-52, anti-Mi-2b), abnormal nailfold capillaroscopy with a scleroderma pattern, interstitial lung disease and cardiac involvement. The overall clinical picture was consistent with the diagnosis of jSSc.

Conclusions

LJM can be the initial sign of underlying systemic sclerosis. Nailfold capillaroscopy may help differentiate jSSc from classical LJM in pediatric patients with T1D and finger contractures or skin induration of no clear origin.

This case report provides a starting point for a novel hypothesis regarding the pathogenesis of jSSc. The association between T1D and jSSc may be more than a coincidence and could suggest a relationship between glucose metabolism, fibrosis and microangiopathy.
Distress and post-traumatic stress in parents of patients with congenital gastrointestinal malformations: a cross-sectional cohort study
Authors: Roorda D. , van der Steeg A. F. W. , van Dijk M. , Derikx J. P. M. , Gorter R. R. , Rotteveel J. , van Goudoever J. B. , van Heurn L. W. E. , Oosterlaan J. , Haverman L. ,   Emma Children’s Hospital Amsterdam UMC Follow-Me Program Consortium
Published: September 2022

Background

Congenital gastrointestinal malformation (CGIM) require neonatal surgical treatment and may lead to disease-specific sequelae, which have a potential psychological impact on parents. The aim of this study is to assess distress and symptoms of post-traumatic stress disorder (PTSD) in parents of patients with CGIM. In this cross-sectional study, seventy-nine parents (47 mothers and 32 fathers) of 53 patients with CGIM completed the Distress Thermometer for Parents (DT-P) and the Self Rating Scale for Posttraumatic Stress Disorders (SRS-PTSD) as part of the multidisciplinary follow-up of their children (aged 5–35 months). Group differences were tested between parents and representative Dutch reference groups with regard to rates of (clinical) distress and PTSD, and severity of overall distress and PTSD, for mothers and fathers separately. Mixed model regression models were used to study factors associated with the risk of (clinical) distress, PTSD and with severity of symptoms of PTSD (intrusion, avoidance and hyperarousal).

Results

Prevalence of clinical distress was comparable to reference groups for mothers (46%) and fathers (34%). There was no difference in severity of overall distress between both mothers as well as fathers and reference groups. Prevalence of PTSD was significantly higher in mothers (23%) compared to the reference group (5.3%) (OR = 5.51,p < 0.001), not in fathers (6.3% vs 2.2.%). Symptoms of intrusion were commonly reported by all the parents (75%). Longer total length of child’s hospital stay was associated with more severe symptoms of intrusion, avoidance and hyperarousal. Child’s length of follow-up was negatively associated with severity of intrusion.

Conclusions

Having a child with CGIM has a huge impact on parents, demonstrated by a higher prevalence of PTSD in mothers, but not fathers, compared to parents in the general population. Monitoring of symptoms of PTSD of parents in follow-up is necessary.
Menorrhagia as main presentation sign of severe hypothyroidism in a pediatric patient: a case report
Authors: Barbero Arianna , Pagano Manuela , Tuli Gerdi , Buganza Raffaele , de Sanctis Luisa , Bondone Claudia
Published: September 2022

Background

The relative high frequency of menstrual irregularities in the first two–three years after menarche may lead to the risk of underestimation of associated pathological conditions, which are always to be accurately researched with careful examination and anamnesis. The association between menstrual irregularities and hypothyroidism is described in literature but the available data are scarce and mainly based on adult case series. It is described that low plasma levels of thyroid hormone can shift the hemostatic system towards a hypocoagulable and hyperfibrinolytic state and seem to lead to an increased bleeding risk.

Case presentation

This case report describes the case of a thirteen years old girl who presented to our Emergency Department complaining of menorrhagia for the last fifteen days, leading to severe anemia. The objective examination revealed clinical signs of hypothyroidism and a severe short stature, lower than mid-parental height, with stunting of growth and a significant bone age delay. Blood exams and thyroid ultrasound were consistent with the diagnosis of severe hypothyroidism in autoimmune thyroiditis with acquired von Willebrand syndrome, growth hormone deficiency. Magnetic resonance showed pituitary functional hyperplasia.

The substitutive therapy with levothyroxine led to the resolution of heavy bleeding after five days and following normalization of coagulative parameters and pituitary hyperplasia.

Conclusions

Hypothyroidism usually presents with unspecific symptoms, with consequent risk of diagnostic delay. It can influence the coagulation system and it seems to be associated to increased risk of menstrual irregularities.

We underline the importance of a regular follow up of the pubertal development, including height measurements, thyroid palpation and menstrual anamnesis to intercept red flags findings for hypothyroidism.
Pathogenesis, diagnosis, dietary management, and prevention of gastrointestinal disorders in the paediatric population
Authors: Pulvirenti Giulio , Sortino Vincenzo , Manti Sara , Parisi Giuseppe Fabio , Papale Maria , Giallongo Alessandro , Leonardi Salvatore
Published: September 2022

Nutrition has a central role in child growth with long-term effects, and nutrition management in gastrointestinal disorders has great importance for child health and disease outcomes. Breast milk is the first choice for infant nutrition. When it is not available, special milk formulas are adopted in specific conditions, as a medical treatment. Moving from the strong guidelines, recommendations and the new possibilities of special diet treatment, this review will analyse the current diet treatment in different gastrointestinal disorders, including food allergy, cystic fibrosis, inflammatory bowel diseases, short-bowel syndrome, gastroesophageal reflux, and eosinophilic esophagitis. The review also aimed at understanding the role of diet and its effects on these diseases. The growth monitoring can prevent malnutrition and improve disease outcomes, particularly in children, and an appropriate dietary management targeted to specific disorders is the best therapeutic choice alone or in combination with pharmacological therapy.
Chest wall loading during supine and prone position in patients with COVID-19 ARDS: effects on respiratory mechanics and gas exchange
Authors: Umbrello Michele , Lassola Sergio , Sanna Andrea , Pace Rocco , Magnoni Sandra , Miori Sara
Published: September 2022

Background

Recent reports of patients with severe, late-stage COVID-19 ARDS with reduced respiratory system compliance described paradoxical decreases in plateau pressure and increases in respiratory system compliance in response to anterior chest wall loading. We aimed to assess the effect of chest wall loading during supine and prone position in ill patients with COVID-19-related ARDS and to investigate the effect of a low or normal baseline respiratory system compliance on the findings.

Methods

This is a single-center, prospective, cohort study in the intensive care unit of a COVID-19 referral center. Consecutive mechanically ventilated, critically ill patients with COVID-19-related ARDS were enrolled and classified as higher (≥ 40 ml/cmH2O) or lower respiratory system compliance (< 40 ml/cmH2O). The study included four steps, each lasting 6 h: Step 1, supine position, Step 2, 10-kg continuous chest wall compression (supine + weight), Step 3, prone position, Step 4, 10-kg continuous chest wall compression (prone + weight). The mechanical properties of the respiratory system, gas exchange and alveolar dead space were measured at the end of each step.

Results

Totally, 40 patients were enrolled. In the whole cohort, neither oxygenation nor respiratory system compliance changed between supine and supine + weight; both increased during prone positioning and were unaffected by chest wall loading in the prone position. Alveolar dead space was unchanged during all the steps. In 16 patients with reduced compliance, PaO2/FiO2 significantly increased from supine to supine + weight and further with prone and prone + weight (107 ± 15.4 vs. 120 ± 18.5 vs. 146 ± 27.0 vs. 159 ± 30.4, respectively; p < 0.001); alveolar dead space decreased from both supine and prone position after chest wall loading, and respiratory system compliance significantly increased from supine to supine + weight and from prone to prone + weight (23.9 ± 3.5 vs. 30.9 ± 5.7 and 31.1 ± 5.7 vs. 37.8 ± 8.7 ml/cmH2O, p < 0.001). The improvement was higher the lower the baseline compliance.

Conclusions

Unlike prone positioning, chest wall loading had no effects on respiratory system compliance, gas exchange or alveolar dead space in an unselected cohort of critically ill patients with C-ARDS. Only patients with a low respiratory system compliance experienced an improvement, with a higher response the lower the baseline compliance.
Three-dimensional in vitro culture models in oncology research
Authors: Jubelin Camille , Muñoz-Garcia Javier , Griscom Laurent , Cochonneau Denis , Ollivier Emilie , Heymann Marie-Françoise , Vallette François M. , Oliver Lisa , Heymann Dominique
Published: September 2022

Cancer is a multifactorial disease that is responsible for 10 million deaths per year. The intra- and inter-heterogeneity of malignant tumors make it difficult to develop single targeted approaches. Similarly, their diversity requires various models to investigate the mechanisms involved in cancer initiation, progression, drug resistance and recurrence. Of the in vitro cell-based models, monolayer adherent (also known as 2D culture) cell cultures have been used for the longest time. However, it appears that they are often less appropriate than the three-dimensional (3D) cell culture approach for mimicking the biological behavior of tumor cells, in particular the mechanisms leading to therapeutic escape and drug resistance. Multicellular tumor spheroids are widely used to study cancers in 3D, and can be generated by a multiplicity of techniques, such as liquid-based and scaffold-based 3D cultures, microfluidics and bioprinting. Organoids are more complex 3D models than multicellular tumor spheroids because they are generated from stem cells isolated from patients and are considered as powerful tools to reproduce the disease development in vitro. The present review provides an overview of the various 3D culture models that have been set up to study cancer development and drug response. The advantages of 3D models compared to 2D cell cultures, the limitations, and the fields of application of these models and their techniques of production are also discussed.
Location-aided uplink transmission for user-centric cell-free massive MIMO systems: a fairness priority perspective
Authors: Wei Chen , Xu Kui , Shen Zhexian , Xia Xiaochen , Xie Wei , Li Chunguo
Published: September 2022

In this paper, we investigate the uplink transmission for user-centric cell-free massive multiple-input multiple-output (MIMO) systems. The largest-large-scale-fading-based access point (AP) selection method is adopted to achieve a user-centric operation. Under this user-centric framework, we propose a novel inter-cluster interference-based (IC-IB) pilot assignment scheme to alleviate pilot contamination. Considering the local characteristics of channel estimates and statistics, we propose a location-aided distributed uplink combining scheme to balance the relationship among the spectral efficiency (SE), user equipment (UE) fairness and complexity, in which local partial minimum mean-squared error (LP-MMSE) combining is adopted for some APs, while maximum-ratio (MR) combining is adopted for the remaining APs. A corresponding AP selection scheme based on a novel proposed metric representing inter-user interference is proposed. We also propose a new fairness coefficient taking SE performance into account to indicate the UE fairness. Moreover, the performance of the proposed scheme is investigated under fractional power control and max–min fairness (MMF) power control. Simulation results demonstrate that the channel estimation accuracy of our proposed IC-IB pilot assignment scheme outperforms that of the conventional pilot assignment schemes. It is also shown that compared with the benchmark LP-MMSE combining, the proposed location-aided combining trades 13.45$$\%$$
%
average SE loss for 26.61$$\%$$
%
UE fairness improvement and 28.58$$\%$$
%
complexity reduction when $$\gamma = 0.6$$

γ
=
0.6

. And by adjusting the threshold $$\gamma$$
γ
, a good trade-off between the average SE, UE fairness and computational complexity can be provided by the proposed scheme. Furthermore, the proposed scheme with fractional power control can better demonstrate the advantages of trade-off performance than MMF power control and full power transmission.
The COVID-19 pandemic and Alzheimer’s disease: mutual risks and mechanisms
Authors: Chen Feng , Chen Yanting , Wang Yongxiang , Ke Qiongwei , Cui Lili
Published: September 2022

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a life-threatening disease, especially in elderly individuals and those with comorbidities. The predominant clinical manifestation of COVID-19 is respiratory dysfunction, while neurological presentations are increasingly being recognized. SARS-CoV-2 invades host cells primarily via attachment of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor expressed on cell membranes. Patients with Alzheimer’s disease (AD) are more susceptible to SARS-CoV-2 infection and prone to severe clinical outcomes. Recent studies have revealed some common risk factors for AD and COVID-19. An understanding of the association between COVID-19 and AD and the potential related mechanisms may lead to the development of novel approaches to treating both diseases. In the present review, we first summarize the mechanisms by which SARS-CoV-2 invades the central nervous system (CNS) and then discuss the associations and potential shared key factors between COVID-19 and AD, with a focus on the ACE2 receptor, apolipoprotein E (APOE) genotype, age, and neuroinflammation.
Benefit with preventive noninvasive ventilation in subgroups of patients at high-risk for reintubation: a post hoc analysis
Authors: Hernández Gonzalo , Vaquero Concepción , Ortiz Ramon , Colinas Laura , de Pablo Raul , Segovia Lourdes , Rodriguez Maria Luisa , Villasclaras Ana , Muñoz-Moreno Juan Francisco , Suarez-Sipmann Fernando , Canabal Alfonso , Cuena Rafael , Roca Oriol
Published: September 2022

Background

High-flow nasal cannula (HFNC) was shown to be non-inferior to noninvasive ventilation (NIV) for preventing reintubation in a general population of high-risk patients. However, some subgroups of high-risk patients might benefit more from NIV. We aimed to determine whether the presence of many risk factors or overweight (body mass index (BMI) ≥ 25 kg/m2) patients could have different response to any preventive therapy, NIV or HFNC in terms of reduced reintubation rate.

Methods

Not pre-specified post hoc analysis of a multicentre, randomized, controlled, non-inferiority trial comparing NFNC and NIV to prevent reintubation in patients at risk for reintubation. The original study included patients with at least 1 risk factor for reintubation.

Results

Among 604 included in the original study, 148 had a BMI ≥ 25 kg/m2. When adjusting for potential covariates, patients with ≥ 4 risk factors (208 patients) presented a higher risk for reintubation (OR 3.4 [95%CI 2.16–5.35]). Patients with ≥ 4 risk factors presented lower reintubation rates when treated with preventive NIV (23.9% vs 45.7%; P = 0.001). The multivariate analysis of overweight patients, adjusted for covariates, did not present a higher risk for reintubation (OR 1.37 [95%CI 0.82–2.29]). However, those overweight patients presented an increased risk for reintubation when treated with preventive HFNC (OR 2.47 [95%CI 1.18–5.15]).

Conclusions

Patients with ≥ 4 risk factors for reintubation may benefit more from preventive NIV. Based on this result, HFNC may not be the optimal preventive therapy in overweight patients. Specific trials are needed to confirm these results.
Brazilian industrial yeasts show high fermentative performance in high solids content for corn ethanol process
Authors: Secches Thaís O. , Santos Viera Carla F. , Pereira Thaynara K. E. , Santos Victor T. O. , Ribeirodos Santos Jade , Pereira Gonçalo A. G. , Carazzolle Marcelo F.
Published: September 2022

An imminent change in the world energy matrix makes it necessary to increase the production of renewable fuels. The United States and Brazil are the world's largest producers, but their production methods are very different, using different raw materials, ground corn and sugarcane juice, respectively. In recent years, strong investments have been made to expand the use of corn in Brazilian ethanol production. The combination of the sugar cane and corn ethanol industries has generated innovations in the sector, such as the "flex" mills, which are traditional sugar cane mills adapted to produce corn ethanol in the sugar cane off-season. Brazil has a portfolio of robust industrial yeasts for sugarcane ethanol production, naturally evolved and selected over the past 50 years. In this work, we analyze for the first time the performance of Brazilian industrial strains (BG-1, CAT-1, PE-2 and SA-1, widely used in sugarcane ethanol production) in corn ethanol production using different stress conditions. Ethanol Red yeast, traditionally used in corn ethanol plants around the world, was used as a control. In terms of tolerance to temperature (35 °C), strains BG-1 and SA-1 stood out. In fermentations with high solids concentration (35%), strain BG-1 reached ethanol contents higher than 19% w/v and had a productivity gain of 5.8% compared to fermentation at 30%. This was the first time that these industrial strains were evaluated using the high solids concentration of 35% and the results point to ways to improve the corn ethanol production process.

Graphical Abstract
Prokaryotes of renowned Karlovy Vary (Carlsbad) thermal springs: phylogenetic and cultivation analysis
Authors: Smrhova Tereza , Jani Kunal , Pajer Petr , Kapinusova Gabriela , Vylita Tomas , Suman Jachym , Strejcek Michal , Uhlik Ondrej
Published: September 2022

Background

The extreme conditions of thermal springs constitute a unique aquatic habitat characterized by low nutrient contents and the absence of human impacts on the microbial community composition. Thus, these springs may host phylogenetically novel microorganisms with potential use in biotechnology. With this hypothesis in mind, we examined the microbial composition of four thermal springs of the world-renowned spa town of Karlovy Vary (Carlsbad), Czechia, which differ in their temperature and chemical composition.

Results

Microbial profiling using 16S rRNA gene sequencing revealed the presence of phylogenetically novel taxa at various taxonomic levels, spanning from genera to phyla. Many sequences belonged to novel classes within the phyla Hydrothermae, Altiarchaeota, Verrucomicrobia, and TA06. Cultivation-based methods employing oligotrophic media resulted in the isolation of 44 unique bacterial isolates. These include strains that withstand concentrations of up to 12% NaClw/v in cultivation media or survive a temperature of 100 °C, as well as hitherto uncultured bacterial species belonging to the genera Thermomonas, Paenibacillus, and Cellulomonas. These isolates harbored stress response genes that allow them to thrive in the extreme environment of thermal springs.

Conclusions

Our study is the first to analyze the overall microbial community composition of the renowned Karlovy Vary thermal springs. We provide insight into yet another level of uniqueness of these springs. In addition to their unique health benefits and cultural significance, we demonstrate that these springs harbor phylogenetically distinct microorganisms with unusual life strategies. Our findings open up avenues for future research with the promise of a deeper understanding of the metabolic potential of these microorganisms.
A novel approach to sclerotomy closure in pars plana vitrectomy: a pilot study
Authors: Suarez Mallory K. , Sappington Rebecca M. , Hayes Bartlett
Published: September 2022

Background

Methods of sclerotomy closure following a vitrectomy, including the use of sutures, have been associated with complications such as inflammation, foreign body sensation, and infection. Here, we test an innovative approach to scleral wound closure following pars plana vitrectomy that involves plugging the wound. We investigated several materials with the intent of using products that were either already approved by the FDA for other types of procedures or were biocompatible patient-derived materials.

Methods

We examined whether scleral wounds could be sealed by a clot or internal “plug” rather than a suture or an external adhesive. We tested patient-derived materials (platelet-rich plasma (PRP) and whole blood) as well as polyethylene glycol (PEG) sealant. Whole blood and PRP were prevented from clotting prematurely using sodium citrate, and were clotted for the study with thrombin. Polyethylene glycol (PEG) sealant was prepared according to manufacturer’s recommendations. We used fresh-frozen cadaveric porcine eyes. We tested several methods to form plugs using the above materials, as well as various methods to deliver the plugs into the sclerotomy incisions. We used a novel technique of manual vitrectomy. Successfully generated and implanted clots were tested for efficacy with the Seidel test.

Results

Polyethylene glycol (PEG) sealant fractured during our attempts at molding and inserting the plug. In contrast, both whole blood and PRP yielded successful plugs for insertion. We molded a whole blood clot plug by allowing it to clot inside a 20-gauge angiocath catheter and we successfully delivered it through a 23G trocar. At baseline, no wound leakage was apparent. However, the whole blood clot dislodged during the Seidel test. We successfully molded and delivered a PRP clot plug using a tapered 2-20 μl pipette tip, using MAXGrip Forceps to push it through into the wound. No scleral wound leakage was noted at our baseline physiologic infusion pressure. Furthermore, the PRP clot plug prevented scleral wound leakage up to a pressure of 60 mmHg and was confirmed with the Seidel test.

Conclusion

Our findings suggest that insertion of a clot plug made from either whole blood or PRP may be an effective strategy for scleral wound closure following pars plana vitrectomy. Further testing in preclinical models is warranted to further refine the materials and methods, since this appears to have the potential to improve the closure of the scleral wounds after pars plana vitrectomy.
Real-world evidence of biologic treatments in psoriatic arthritis in Italy: results of the CHRONOS (EffeCtiveness of biologic treatments for psoriatic artHRitis in Italy: an ObservatioNal lOngitudinal Study of real-life clinical practice) observational longitudinal study
Authors: Colombo Delia , Frassi Micol , Pagano Mariano Giusy , Fusaro Enrico , Lomater Claudia , Del Medico Patrizia , Iannone Florenzo , Foti Rosario , Limonta Massimiliano , Marchesoni Antonio , Raffeiner Bernd , Viapiana Ombretta , Grassi Walter , Grembiale Rosa Daniela , Guggino Giuliana , Mazzone Antonino , Tirri Enrico , Perricone Roberto , Sarzi Puttini Pier Carlo , De Vita Salvatore , Conti Fabrizio , Ori Alessandra , Simoni Lucia , Fiocchi Martina , Orsenigo Roberto , Zagni Emanuela ,   and the CHRONOS Study Group, Frassi Micol , Caminiti Maurizio , Fusaro Enrico , Lomater Claudia , Del Medico Patrizia , Iannone Florenzo , Foti Rosario , Limonta Massimiliano , Marchesoni Antonio , Raffeiner Bernd , Viapiana Ombretta , Grassi Walter , Grembiale Rosa Daniela , Guggino Giuliana , Mazzone Antonino , Tirri Enrico , Perricone Roberto , Puttini Pier Carlo Sarzi , De Vita Salvatore , Conti Fabrizio
Published: September 2022

Background

Biologics have demonstrated efficacy in PsA in randomized clinical trials. More evidence is needed on their effectiveness under real clinical practice conditions. The aim of the present work is to provide real-world evidence of the effectiveness of biologics for PsA in the daily clinical practice.

Methods

CHRONOS was a multicenter, non-interventional, cohort study conducted in 20 Italian hospital rheumatology clinics.

Results

399 patients were eligible (56.9% females, mean (SD) age: 52.4 (11.6) years). The mean (SD) duration of PsA and psoriasis was 7.2 (6.9) and 15.3 (12.2) years, respectively. The mean (SD) duration of the biologic treatment under analysis was 18.6 (6.5) months. The most frequently prescribed biologic was secukinumab (40.4%), followed by adalimumab (17.8%) and etanercept (16.5%). The proportion of overall responders according to EULAR DAS28 criteria was 71.8% (95% CI: 66.7–76.8%) out of 308 patients at 6 months and 68.0% (95% CI: 62.7–73.3%) out of 297 patients at 1 year. Overall, ACR20/50/70 responses at 6 months were 41.2% (80/194), 29.4% (57/194), 17.1% (34/199) and at 1-year were 34.9% (66/189), 26.7% (51/191), 18.4% (36/196), respectively. Secondary outcome measures improved rapidly already at 6 months: mean (SD) PASI, available for 87 patients, decreased from 3.2 (5.1) to 0.6 (1.3), the proportion of patients with dactylitis from 23.6% (35/148) to 3.5% (5/142) and those with enthesitis from 33.3% (49/147) to 9.0% (12/133).

Conclusions

The CHRONOS study provides real-world evidence of the effectiveness of biologics in PsA in the Italian rheumatological practice, confirming the efficacy reported in RCTs across various outcome measures.
Antithrombotic treatment and outcome after endovascular treatment and acute carotid artery stenting in stroke patients with atrial fibrillation
Authors: Weller Johannes M. , Dorn Franziska , Meissner Julius N. , Stösser Sebastian , Beckonert Niklas M. , Nordsiek Julia , Kindler Christine , Riegler Christoph , Keil Fee , Petzold Gabor C. , Bode Felix J. ,   the GSR-ET investigators, Reich A. , Nikoubashman O. , Röther J. , Eckert B. , Braun M. , Hamann G. F. , Siebert E. , Nolte C. H. , Bohner G. , Eckert R. M. , Borggrefe J. , Schellinger P. , Berrouschot J. , Bormann A. , Kraemer C. , Leischner H. , Petersen M. , Stögbauer F. , Boeck-Behrens T , Wunderlich S. , Ludolph A. , Henn K. H. , Gerloff C. , Fiehler J. , Thomalla G. , Alegiani A. , Schäfer J. H. , Tiedt S. , Kellert L. , Trumm C. , Ernemann U. , Poli S. , Liman J. , Ernst M. , Gröschel K. , Uphaus T.
Published: September 2022

Background

Oral anticoagulation (OAC) is the mainstay of secondary prevention in ischemic stroke patients with atrial fibrillation (AF). However, in AF patients with large vessel occlusion stroke treated by endovascular therapy (ET) and acute carotid artery stenting (CAS), the optimal antithrombotic medication remains unclear.

Methods

This is a subgroup analysis of the German Stroke Registry—Endovascular Treatment (GSR-ET), a prospective multicenter cohort of patients with large vessel occlusion stroke undergoing ET. Patients with AF and CAS during ET were included. We analyzed baseline and periprocedural characteristics, antithrombotic strategies and functional outcome at 90 days.

Results

Among 6635 patients in the registry, a total of 82 patients (1.2%, age 77.9 ± 8.0 years, 39% female) with AF and extracranial CAS during ET were included. Antithrombotic medication at admission, during ET, postprocedural and at discharge was highly variable and overall mortality in hospital (21%) and at 90 days (39%) was high.

Among discharged patients (n = 65), most frequent antithrombotic regimes were dual antiplatelet therapy (DAPT, 37%), single APT + OAC (25%) and DAPT + OAC (20%). Comparing DAPT to single or dual APT + OAC, clinical characteristics at discharge were similar (median NIHSS 7.5 [interquartile range, 3–10.5] vs 7 [4–11], p = 0.73, mRS 4 [IQR 3–4] vs. 4 [IQR 3–5], p = 0.79), but 90-day mortality was higher without OAC (32 vs 4%, p = 0.02).

Conclusions

In AF patients who underwent ET and CAS, 90-day mortality was higher in patients not receiving OAC.

Registration: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.
Association between social support and pregnancy stress: a cross-sectional study of neighbors’ interactions
Authors: Abdi Sadaf , Faramarzi Mahbobeh , Bouzari Zinatossadat , Chehrazi Mohammad , Esfandyari Maria
Published: September 2022

Background

Pregnancy is associated with substantial stressful experiences. There are controversies concerning the positive and negative roles of social support during pregnancy. This research aimed to study the association of social support with the pregnancy-related stress.

Methods

In the current cross-sectional research, 200 pregnant women were recruited through convenience sampling from two teaching hospitals affiliated with Babol University of Medical Sciences and a private obstetric clinic. The women completed two self-reported questionnaires during prenatal care appointments. The questionnaires included the Revised Prenatal Distress Questionnaire (NuPDQ) and Social Support Questionnaire (SSQ).

Results

A significantly positive association was observed between the social support of neighbors and the total score of pregnancy stress (P<0.001), as well as the scores of its four subscales, namely medical problems (P<0.001), parenting (P=0.25), infant health stress (P=0.006), and pregnancy symptoms (P=0.001). Based on the linear regression models, the social support of neighbors was significantly related to the medical problem-associated stress in pregnant women (β = 0.147, 95% CI: 0.14 to 0.62, p = 0.047), pregnancy symptom (β = 0.203, 95% CI: −0.01 to 0.327, p = 0.017), and fear of childbirth (β = 0.164, 95% CI: 0.05 to 0.38, p = 0.046). Furthermore, the neighbors’ social support (β = 0.172, 95% CI: 0.02 to 0.32, p = 0.04) and the total score of social support (β = 0.155, 95% CI: 0.01 to 0.304, p = 0.046) were significantly associated with the total score of pregnancy stress.

Conclusions

Neighbors’ support, as a component of social support, was found to be significantly related to pregnancy stress. This study recommends that healthcare providers consider the positive and negative impacts of social support during the pregnancy period.
Computational analysis of G-protein-coupled receptor kinase family members as potential targets for colorectal cancer therapy
Authors: Hermawan Adam , Putri Herwandhani
Published: September 2022

Background

G-protein-coupled receptor (GPCR) kinases (GRKs) interact with ligand-activated GPCR, causing intracellular phosphorylation and interfering with the intracellular signal transduction associated with the development of cancer. Colorectal cancer (CRC) is a fast-growing disease, and its molecular mechanism involves various regulatory proteins, including kinases. However, the GRK mechanism in CRC has not been explored.

Methods

We used an integrated computational approach to investigate the potential of GRK family members as targeted proteins in CRC. The GRK expression levels in tumor and normal tissues, colon adenocarcinoma samples, and metastatic colon adenocarcinoma were analyzed using ONCOMINE, GEPIA, and UALCAN, as well as TNM plots. Genetic changes in the GRK family genes were investigated using cBioportal. The prognostic value related to the gene expression of the GRK family was examined using GEPIA and UALCAN. Co-expression analysis of the GRK family was conducted using COXPRESdb. Association analysis of the Gene Ontology, KEGG pathway enrichment, and drug-gene analyses were performed using the over-representation analysis (ORA) in WebGestalt.

Results

GRK2, GRK3, and GRK5 mRNA levels increased significantly in patients with CRC and metastatic CRC. Genetic changes were detected in patients with CRC, including GRK7 (1.1%), GRK2 (1.7%), GRK4 (2.3%), GRK5 (2.5%), GRK6 (2.5%), GRK3 (2.9%), and GRK1 (4%). CRC patients with low mRNA of GRK7 levels had better disease-free and overall survival than those with high GRK7 levels. Hierarchical clustering analysis revealed significant positive correlations between GRK5 and GRK2 and between GRK2 and GRK6. KEGG pathway enrichment analysis showed that the gene network (GN) regulated several cellular pathways, such as the morphine addiction signaling and chemokine signaling pathways in cancer. The drug-gene association analysis indicated that the GN was associated with several drugs, including reboxetine, pindolol, beta-blocking agents, and protein kinase inhibitors.

Conclusion

No research has been conducted on the relation of GRK1 and GRK7 to cancer, particularly CRC. In this work, genes GRK2, GRK3, GRK5, and GRK6 were found to be oncogenes in CRC. Although inhibitors against GRK2, GRK5, and GRK6 have previously been developed, further research, particularly preclinical and clinical studies, is needed before these agents may be used to treat CRC.
Impact of paediatric intensive care unit admission on neurocognitive function in children
Authors: Zaitoun Raghda , Aly Rasha Hussein , Rezk Ahmed R.
Published: September 2022

Background

Advances in paediatric critical care have resulted in a reduction in mortality. This has shifted the focus to paediatric intensive care unit (PICU)-related morbidities and how to reduce or prevent them. In this study, we aimed to study the impact of paediatric intensive care unit (PICU) admission on neurocognitive performance.

Methods

Intelligence quotient (IQ) was tested in 50 children (27 boys, 23 girls; mean age 6.98 years) 3 months after PICU discharge and in 75 controls using the Stanford-Binet IQ test.

Results

There was no statistically significant difference between patients and controls with regard to IQ scores, and no difference between medical and surgical patients (p > 0.05). IQ was unaffected by sedation, blood transfusion, or blood product transfusion. Patients who underwent a major surgical procedure, needed inotropic support, and needed mechanical ventilation had non-significantly lower IQ scores than those who did not. A non-significant negative correlation was observed between the length of PICU stay, mechanical ventilation duration, sedative use, and inotropic support.

Conclusions

PICU admission does not appear to significantly affect cognitive outcomes in paediatric survivors.
Medication-related burden among Iraqi patients with rheumatoid arthritis: An observational study
Authors: Kadhim Jwad Rwnk , Jabbar Kadhim Dheyaa , Hadi Munshed Alosami Mohammed , G. Shareef Laith
Published: September 2022

Background: Rheumatoid arthritis (RA) is a chronically progressing inflammatory disease having articular, extra-articular, and systemic manifestations of unclear origin. Medication-related burden (MRB) is a novel concept that focuses on unpleasant feelings associated with the therapeutic process. The purpose of this research was to examine MRB among Iraqi patients with rheumatoid arthritis from the patient's viewpoint.

Methods: The present research was a cross-sectional study conducted on patients with rheumatoid arthritis who had previously been diagnosed and visited Baghdad Teaching Hospital/Medical City/Rheumatology department between December 2021 through March 2022. The Living with Medicines Questionnaire was used to assess MRB (LMQ).

Results: The study recruited 250 RA patients. The average age of the patients was 47.29± 12.72 years. The vast majority were women, 80.8%. The mean LMQ score was 113.78± 13.95. Most participants experienced a moderate degree of burden of 72.0%, followed by a minimum commitment of 24.4%, a high burden of 2.8%, and no burden of 0.8%, with no patient experiencing a high burden of 0 %. Women had significantly higher medication-related burdens (total LMQ). RA patients with more than five chronic medications had substantially higher MRB than those with fewer scheduled medications. Patients with chronic diseases (other than RA) had significantly higher MRB than those without other chronic diseases. The total LMQ score had a significant positive correlation with the Clinical Disease Activity Index (CDAI) value. In other words, when disease severity increases, the MRB increases.

Conclusion: A considerable proportion of the RA patients involved in the current study have experienced MRB. Female sex, polypharmacy, comorbidities, and more severe disease are associated with more MRB.
Radiotherapy in the comprehensive treatment of rectal cancer
Authors: Luts B.
Published: September 2022

Introduction. A favorable outcome of the treatment of patients with rectal cancer in the early stages is not a difficult task, as it is easily solved thanks to only surgical intervention. The biggest problem is the treatment of patients with late-stage (III and IV) rectal cancer. The use of radiation therapy is an integral niche in the complex treatment of rectal cancer. Complete or partial clinical response of the tumor to neoadjuvant therapy is a favorable factor that correlates with an increase in overall and recurrence-free survival of patients with rectal cancer.

Aim. To conduct an analysis of the effectiveness of radiotherapy and neoadjuvant chemoradiotherapy in the complex treatment of rectal cancer based on the results of the tumor's clinical response to the treatment.

Research results. In both groups of  patients, the tumor was localized in the middle ampullary part of the rectum in 52.6% of the main group and 55.4% of the control group. In the lower ampullary section of the rectum in 22 patients of the main group (38.6%) and in 22 (39.3%) of the control group, respectively. The number of patients with tumor localization in the upper ampullary region was 5 (8.8%) and 35 (5.3%), respectively. Positive dynamics in the form of replacement of tumor tissue by fibrosis was observed in 89 (78.7%) patients in the compared groups. A complete clinical response was noted in 2 (3.5%) patients in the main group and in 1 (1.8%) in the control group. In 86 patients in the compared groups, II and III degrees of tumor regression according to TRG grading were recorded in 43 (75.4%) patients in the main group and 43 (76.8%) in the control group.

Conclusions. In both groups, the tumor was most often localized in the middle ampullary part of the rectum, 52.6% in the main group and 55.4% of the control group. Positive dynamics in the form of replacement of tumor tissue by fibrosis was observed in 89 (78.7%) patients in the compared groups. A complete clinical response was noted in 2 (3.5%) patients in the main group and in 1 (1.8%) in the control group. Unsatisfactory dynamics in the form of IV and V degrees of tumor regression according to the TRG grading were noted in 12 (21.05%) patients of the main group and in 12 (21.4%) - in the control group.