bluuebunny/crossref_metadata_2025 huggingface dataset:
The targetable nanoparticle BAF312@cRGD-CaP-NP represses tumor growth and angiogenesis by downregulating the S1PR1/P-STAT3/VEGFA axis in triple-negative breast cancer
Authors: Gong Ke , Jiao Juyang , Xu Chaoqun , Dong Yang , Li Dongxiao , He Di , Zhao De , Yu Jian , Sun Ying , Zhang Wei , Bai Min , Duan Yourong
Published: May 2021

Background

Overexpressed vascular endothelial growth factor A (VEGFA) and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) cause unrestricted tumor growth and angiogenesis of breast cancer (BRCA), especially triple-negative breast cancer (TNBC). Hence, novel treatment strategy is urgently needed.

Results

We found sphingosine 1 phosphate receptor 1 (S1PR1) can regulate P-STAT3/VEGFA. Database showed S1PR1 is highly expressed in BRCA and causes the poor prognosis of patients. Interrupting the expression of S1PR1 could inhibit the growth of human breast cancer cells (MCF-7 and MDA-MB-231) and suppress the angiogenesis of human umbilical vein endothelial cells (HUVECs) via affecting S1PR1/P-STAT3/VEGFA axis. Siponimod (BAF312) is a selective antagonist of S1PR1, which inhibits tumor growth and angiogenesis in vitro by downregulating the S1PR1/P-STAT3/VEGFA axis. We prepared pH-sensitive and tumor-targeted shell-core structure nanoparticles, in which hydrophilic PEG2000 modified with the cyclic Arg-Gly-Asp (cRGD) formed the shell, hydrophobic DSPE formed the core, and CaP (calcium and phosphate ions) was adsorbed onto the shell; the nanoparticles were used to deliver BAF312 (BAF312@cRGD-CaP-NPs). The size and potential of the nanoparticles were 109.9 ± 1.002 nm and − 10.6 ± 0.056 mV. The incorporation efficacy for BAF312 was 81.4%. Results confirmed BAF312@cRGD-CaP-NP could dramatically inhibit tumor growth and angiogenesis in vitro and in MDA-MB-231 tumor-bearing mice via downregulating the S1PR1/P-STAT3/VEGFA axis.

Conclusions

Our data suggest a potent role for BAF312@cRGD-CaP-NPs in treating BRCA, especially TNBC by downregulating the S1PR1/P-STAT3/VEGFA axis.

Graphic abstract
Urinary vitamin D-binding protein as a marker of ovarian reserve
Authors: Li Sanglin , Hu Lina , Zhang Chanyu
Published: June 2021

Background

Ovarian reserve reflects the quality and quantity of available oocytes and has become an indispensable measure for the better understanding of reproductive potential. Proteomic approaches are especially helpful in discerning differential protein expression patterns associated with normal and diseased states and, thus, proteomic analyses are increasingly used to identify clinically useful biomarkers. The aim of this study was to investigate proteins secreted in the urine of patients with different ovarian reserve by proteomic techniques to identify potential markers for assessing ovarian reserve.

Methods

Urine samples were obtained from patients with polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR), and from normal control (NC)participants. We used isobaric tags for relative and absolute quantification (iTRAQ) technology combined with mass spectrometry analysis to identify candidate urinary proteins in the three groups. The selected proteins were confirmed using western blot analysis and enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic analysis.

Results

When Compared with NC samples, 285 differentially expressed proteins (DEPs) were identified in the DOR samples and 372 in the PCOS samples. By analyzing the intersection of the two groups of DEPs, we found 26 proteins with different expression trends in the DOR and PCOS groups. Vitamin D-binding protein (VDBP) was the key protein for the protein-protein interaction network. ELISA quantification of urinary VDBP revealed the highest levels in the PCOS group, followed by the NC group and the lowest levels in the DOR group (115.90 ± 26.02, 81.86 ± 23.92 and 52.84 ± 21.37 ng/ml, respectively; P < 0.05). As a diagnostic marker, VDBP had a sensitivity of 67.4% and a specificity of 91.8% for DOR, and a sensitivity of 93.8% and a specificity of 77.6% for PCOS.

Conclusions

Urinary VDBP is closely associated with ovarian reserve and can be considered as a novel noninvasive biomarker of ovarian reserve. However, studies including large sample sizes are needed to validate these results.
Coagulopathy and its associated factors among patients with a bleeding diathesis at the University of Gondar Specialized Referral Hospital, Northwest Ethiopia
Authors: Aynalem Melak , Shiferaw Elias , Gelaw Yemataw , Enawgaw Bamlaku
Published: June 2021

Background

Coagulopathy is the major cause of mortality and morbidity throughout the world. Globally, about 26–45% of healthy people have a history of bleeding symptoms, which may be a result of thrombocytopenia, factor deficiency, or pathological inhibitory.

Objective

To assess coagulopathy and its associated factors among patients with bleeding diathesis at the University of Gondar Specialized Referral Hospital from January to May 2020.

Method

A cross-sectional study was conducted on 384 study participants with bleeding diathesis recruited by using a convenient sampling technique. Socio-demographic and clinical characteristics were collected by using questioners. Then 6 ml venous blood was collected with a needle and syringe method. About 3 ml blood was transferred to EDTA test tube for platelet count and 2.7 ml blood was transferred to a test tube containing 0.3 ml of 3.2% sodium citrated anticoagulant for coagulation test. For those study participants with prolonged coagulation tests, a mixing test was done. Blood film and stool examination were also done for malaria and intestinal parasite identification, respectively. The data were entered into EPI-Info version 3.5.3 and then transferred to SPSS version-20 for analysis. Descriptive statistics were summarized as percentages, means, and standard deviations. Bivariate and multivariate logistic regression was used to identify the associated factors, and aP-value less than 0.05 was considered statistically significant.

Results

In this study, the prevalence of coagulopathy was 253/384 (65.9%; 95% CI: 61.16, 70.64). From them, 21.3% (54/253), 51.4% (130/253), and 27.3% (69/253) had only thrombocytopenia, only prolonged coagulation test, and mixed abnormality, respectively. Among participants with prolonged coagulation time, the prevalence of factor deficiency was 21.1% (42/199). Cardiac disease (AOR = 4.80; 95% CI: 2.65, 23.1), and other chronic diseases (AOR = 8.1; 95% CI: 1.84, 35.58) were significantly associated with coagulopathy.

Conclusion

In this study, coagulopathy due to inhibitory was a public health problem. The participants with cardiac and other chronic diseases were at high risk for coagulopathy. Therefore, mixing tests could be done for all prolonged coagulation tests and it could be considered as a routine laboratory test.
Measuring attentiveness toward oral care needs: a comparative study of Indonesian care workers in Japan and Indonesia
Authors: Hirano Yuko O. , Nugraha Susiana , Shiozu Hiroyasu , Higashijima Misako , Rahardjo Tri Budi W.
Published: June 2021

Background

Japan has opened its labor market to care workers from Indonesia under the Japan–Indonesia Economic Partnership Agreement (EPA). However, few studies have examined the types of care skills transferred between countries. We therefore analyzed Indonesian care workers employed in Japan and Indonesia to identify discrepancies in their attentiveness toward oral care in older adults.

Methods

A checklist comprising 42 items of universal oral care assessment was developed prior to the study and distributed via the Internet to 418 Indonesian EPA care workers in Japan and via a paper survey to 213 Indonesian care workers in Indonesia. The Mann–Whitney U test was used to compare the distribution of scores for each checklist item for each group.

Results

The respondents were 110 Japan-based EPA care workers (response rate: 26.3%) and 213 Indonesia-based care workers (response rate: 99.1%). Japan-based care workers were significantly more likely to perform environmental observations of their older adult patients (p < 0.001) and to check items on the oral care checklist during feeding (p < 0.001) and post-meal (p = 0.001), while Indonesia-based care workers were more likely to check the overall condition of patients before meals (p = 0.021).

Conclusions

Discrepancies in checking oral care between the two groups were attributed to the differences in laws and regulations governing the care environments. Indonesian care workers employed in Japan have the advantage of learning to employ a more systematic approach in caring for older adults, in accordance with Japan’s Long-Term Care Act. This approach could contribute toward lowering the risk of aspiration pneumonia in Indonesia. A training program designed for returning migrant workers to transfer newly developed oral care skills will thus be essential for Indonesia to diminish the negative impacts of its aging population.
PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through the inhibition of TM4 (UBAC2) degradation
Authors: Chen Lili , Ye Kuanping , Feng Xiaocheng , Li Lianxi , Li Qin , Huang Ying , Wang Xuanchun , Li Rumei , Hu Cheng , Yang Zhen , Lu Bin , Yang Yehong , Wen Jie , Zhang Zhaoyun , He Min , Wang Qinghua , Zhou Wenbai , Li Yintao , Liu Naijia , Huang Jinya , Shen Qiwei , Yao Qiyuan , Hu Renming
Published: June 2021

Background

The TM4 (UBAC2) protein, which contains 4 transmembrane domains and one ubiquitin binding domain, is mainly expressed in cell and nuclear membranes. The current research aimed to explore the role of TM4 in metabolic inflammation and to examine whether the ubiquitin–proteasome inhibitor PS-341 could regulate the function of TM4.

Methods

The metabolic phenotypes of TM4 knockout (KO) mice were studied. We next explored the association between the polymorphisms of TM4 and obesity in a Chinese Han population. TM4 expression in the visceral fat of obese patients who underwent laparoscopic cholecystectomy was also analysed. Finally, the effect of PS-341 on the degradation and function of the TM4 protein was investigated in vivo and in vitro.

Results

TM4 KO mice developed obesity, hepatosteatosis, hypertension, and glucose intolerance under a high-fat diet. TM4 counterregulated Nur77, IKKβ, and NF-kB both in vivo and in vitro. The TM4 SNP rs147851454 is significantly associated with obesity after adjusting for age and sex (OR 1.606, 95% CI 1.065–2.422 P = 0.023) in 3394 non-diabetic and 1862 type 2 diabetic adults of Han Chinese. TM4 was significantly downregulated in the visceral fat of obese patients. PS-341 induced TM4 expression through inhibition of TM4 degradation in vitro. In db/db mice, PS-341 administration led to downregulation of Nur77/IKKβ/NF-κB expression in visceral fat and liver, and alleviation of hyperglycaemia, hypertension, and glucose intolerance. The hyperinsulinaemic-euglycaemic clamp demonstrated that PS-341 improved the glucose infusion rate and alleviated insulin resistance in db/db mice.

Conclusions

PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through inhibition of TM4 degradation.
The energy-spectrum of bicompatible sequences
Authors: Huang Fenix W. , Barrett Christopher L. , Reidys Christian M.
Published: June 2021

Background

Genotype-phenotype maps provide a meaningful filtration of sequence space and RNA secondary structures are particular such phenotypes. Compatible sequences, which satisfy the base-pairing constraints of a given RNA structure, play an important role in the context of neutral evolution. Sequences that are simultaneously compatible with two given structures (bicompatible sequences), are beacons in phenotypic transitions, induced by erroneously replicating populations of RNA sequences. RNA riboswitches, which are capable of expressing two distinct secondary structures without changing the underlying sequence, are one example of bicompatible sequences in living organisms.

Results

We present a full loop energy model Boltzmann sampler of bicompatible sequences for pairs of structures. The sequence sampler employs a dynamic programming routine whose time complexity is polynomial when assuming the maximum number of exposed vertices,$$\kappa $$κ, is a constant. The parameter$$\kappa $$κdepends on the two structures and can be very large. We introduce a novel topological framework encapsulating the relations between loops that sheds light on the understanding of$$\kappa $$κ. Based on this framework, we give an algorithm to sample sequences with minimum$$\kappa $$κon a particular topologically classified case as well as giving hints to the solution in the other cases. As a result, we utilize our sequence sampler to study some established riboswitches.

Conclusion

Our analysis of riboswitch sequences shows that a pair of structures needs to satisfy key properties in order to facilitate phenotypic transitions and that pairs of random structures are unlikely to do so. Our analysis observes a distinct signature of riboswitch sequences, suggesting a new criterion for identifying native sequences and sequences subjected to evolutionary pressure. Our free software is available at:https://github.com/FenixHuang667/Bifold.
Differences in health care experiences between rare cancer and common cancer patients: results from a national cross-sectional survey
Authors: de Heus Eline , Engelen Vivian , Dingemans Irene , Richel Carol , Schrieks Marga , van der Zwan Jan Maarten , Besselink Marc G. , van Berge Henegouwen Mark I. , van Herpen Carla M. L. , Duijts Saskia F. A.
Published: June 2021

Background

Patients with rare cancers face challenges in the diagnostic and treatment phase, and in access to clinical expertise. Since studies on health care experiences of these patients in comparison to patients with more common cancers are scarce, we aimed to explore these differences.

Methods

Data were cross-sectionally collected among (former) adult cancer patients through a national online survey in the Netherlands (October 2019). Descriptive statistics were reported and subgroups (rare vs. common patients) were compared.

Results

In total, 7343 patients (i.e., 1856 rare and 5487 common cancer patients) participated. Rare cancer patients were more often diagnosed and treated in different hospitals compared to common cancer patients (67% vs. 59%, p < 0.001). Rare cancer patients received treatment more often in a single hospital (60% vs. 57%, p = 0.014), but reported more negative experiences when treated in multiple hospitals than common cancer patients (14% vs. 9%, p < 0.001). They also more often received advise from their physician about the hospital to go to for a second opinion (50% vs. 36%, p < 0.001), were more likely to choose a hospital specialized in their cancer type (33% vs. 22%, p < 0.001), and were more willing to travel as long as necessary to receive specialized care than common cancer patients (55% vs. 47%, p < 0.001).

Conclusions

Rare and common cancer patients differ in their health care experiences. Health care for rare cancer patients can be further improved by proper referral to centers of expertise and building a clinical network specifically for rare cancers.
Effects of early extubation followed by noninvasive ventilation versus standard extubation on the duration of invasive mechanical ventilation in hypoxemic non-hypercapnic patients: a systematic review and individual patient data meta-analysis of randomized controlled trials
Authors: Vaschetto Rosanna , Pecere Alessandro , Perkins Gavin D. , Mistry Dipesh , Cammarota Gianmaria , Longhini Federico , Ferrer Miguel , Pletsch-Assunção Renata , Carron Michele , Moretto Francesca , Qiu Haibo , Della Corte Francesco , Barone-Adesi Francesco , Navalesi Paolo
Published: June 2021

Background

Usefulness of noninvasive ventilation (NIV) in weaning patients with non-hypercapnic hypoxemic acute respiratory failure (hARF) is unclear. The study aims to assess in patients with non-hypercapnic hARF, the efficacy of NIV after early extubation, compared to standard weaning.

Methods

In this individual patient data meta-analysis, we searched EMBASE, Medline and Cochrane Central Register of Controlled Trials to identify potentially eligible randomized controlled trials published from database inception to October 2020. To be eligible, studies had to include patients treated with NIV after early extubation and compared to conventional weaning in adult non-hypercapnic hARF patients. Anonymized individual patient data from eligible studies were provided by study investigators. Using one-step and two-step meta-analysis models we tested the difference in total days spent on invasive ventilation.

Results

We screened 1605 records. Six studies were included in quantitative synthesis. Overall, 459 participants (mean [SD] age, 62 [15] years; 269 [59%] males) recovering from hARF were included in the analysis (233 in the intervention group and 226 controls). Participants receiving NIV had a shorter duration of invasive mechanical ventilation compared to control group (mean difference, − 3.43; 95% CI − 5.17 to − 1.69 days, p < 0.001), a shorter duration of total days spent on mechanical ventilation (mean difference, − 2.04; 95% CI − 3.82 to − 0.27 days, p = 0.024), a reduced risk of ventilatory associated pneumonia (odds ratio, 0.24; 95% CI 0.08 to 0.71, p = 0.014), a reduction of time spent in ICU (time ratio, 0.81; 95% CI 0.68 to 0.96, p = 0.015) and in-hospital (time ratio, 0.81; 95% CI 0.69 to 0.95, p = 0.010), with no difference in ICU mortality.

Conclusions

Although primary studies are limited, using an individual patient data metanalysis approach, NIV after early extubation appears useful in reducing total days spent on invasive mechanical ventilation.

Trial registration

The protocol was registered to PROSPERO database on 12/06/2019 and available at PROSPERO website inserting the study code i.e., CRD42019133837.
Advancing precision public health using human genomics: examples from the field and future research opportunities
Authors: Roberts Megan C. , Fohner Alison E. , Landry Latrice , Olstad Dana Lee , Smit Amelia K. , Turbitt Erin , Allen Caitlin G.
Published: June 2021

Precision public health is a relatively new field that integrates components of precision medicine, such as human genomics research, with public health concepts to help improve population health. Despite interest in advancing precision public health initiatives using human genomics research, current and future opportunities in this emerging field remain largely undescribed. To that end, we provide examples of promising opportunities and current applications of genomics research within precision public health and outline future directions within five major domains of public health: biostatistics, environmental health, epidemiology, health policy and health services, and social and behavioral science. To further extend applications of genomics within precision public health research, three key cross-cutting challenges will need to be addressed: developing policies that implement precision public health initiatives at multiple levels, improving data integration and developing more rigorous methodologies, and incorporating initiatives that address health equity. Realizing the potential to better integrate human genomics within precision public health will require transdisciplinary efforts that leverage the strengths of both precision medicine and public health.
Presence of plasmid-mediated quinolone resistance (PMQR) genes in non-typhoidal Salmonella strains with reduced susceptibility to fluoroquinolones isolated from human salmonellosis in Gyeonggi-do, South Korea from 2016 to 2019
Authors: Lee Sohyun , Park Nanjoo , Yun Sujung , Hur Eunseon , Song Jiwon , Lee Hanna , Kim Yongsug , Ryu Sangryeol
Published: June 2021

Non-typhoidal salmonellosis remains a pressing public health problem worldwide. Quinolones, particularly fluoroquinolones, are widely used to treat various infections, including non-typhoidal salmonellosis, which can be a serious illness. The emergence of fluoroquinolone-resistant Salmonella has resulted in treatment failure and high mortality rates. In this study, we estimated the presence of plasmid-mediated quinolone resistance (PMQR) genes in Salmonella enterica isolated from human salmonellosis patients in South Korea from 2016 to 2019. We evaluated the association of these genes with fluoroquinolone susceptibility. Antimicrobial susceptibility tests for Salmonella isolates were performed using the Vitek II system, and the minimum inhibitory concentrations (MIC) of ciprofloxacin and levofloxacin were determined using the E-test method. Plasmid-mediated quinolone resistance (PMQR) genes were detected by PCR amplification and quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes were analyzed following Sanger sequencing of the PCR products. Thirty-four Salmonella strains with reduced susceptibility to fluoroquinolones (ciprofloxacin MIC ≥ 0.125 µg/mL and levofloxacin MIC ≥ 0.25 µg/mL) were selected from 208 human clinical Salmonella isolates. Among them, 22 Salmonella strains harbored one PMQR gene (qnrA, qnrB, or qnrS), and three Salmonella strains carried two PMQR genes (qnrS and aac(6′)-Ib-cr or qnrA and qnrB). qnrS was the most common PMQR gene. Serotyping revealed that Salmonella 4,[5]12:i:- (32.4%, 11/34) and Salmonella Typhimurium (29.4%, 10/34) were the two most predominant serovars, and Multi-locus sequence typing (MLST) showed that ST19 and ST34 were the most frequent sequence types. In conclusion, qnr gene-positive Salmonella 4,[5],12:i:- and Salmonella Typhimurium were the main serovars responsible for reduced susceptibility to fluoroquinolones. Therefore, our findings suggest that PMQR-positive Salmonella strains, which can be isolated from various samples including human, food, and the environment, should be carefully monitored.
Effect of liquid volume and microflora source on degradation rate and microbial community in corn stover degradation
Authors: Wang Jingjing , Zhu Dan , Zhao Siqi , Xu Song , Yang Rong , Zhao Wei , Zhang Xiaoxia , Huang Zhiyong
Published: June 2021

Degradation is the bottleneck in the utilization of crop straw. In this paper, we screened the microbial consortia degrading corn stover from straw degrading consortia MC1 (M), sheep feces (Y), and mixtures (Q) of M, Y, and cattle feces. The effects of microflora source and liquid volume (representing dissolved oxygen) on the microbial community and degradation rate of corn stover were investigated. The results showed that the degradation rate and cellulase activity of a 200 mL liquid volume (L2) were significantly higher than that of 100 mL (L1). Microflora source had a significant effect on bacterial and fungal diversity, composition and taxa. Q and Y had higher bacterial and fungal α-diversity than that of M. The degradation rate was significantly correlated with cellulase activity but not with microbial diversity. This indicated that liquid volume had a significant effect on degradation rate while microflora source had a significant effect on microbial community in corn stover degradation.
Performance evaluation and analysis of distributed multi-agent optimization algorithms with sparsified directed communication
Authors: Fodor Lidija , Jakovetić Dušan , Krejić Nataša , Jerinkić Nataša Krklec , Škrbić Srđan
Published: June 2021

There has been significant interest in distributed optimization algorithms, motivated by applications in Big Data analytics, smart grid, vehicle networks, etc. While there have been extensive theory and theoretical advances, a proportionally small body of scientific literature focuses on numerical evaluation of the proposed methods in actual practical, parallel programming environments. This paper considers a general algorithmic framework of first and second order methods with sparsified communications and computations across worker nodes. The considered framework subsumes several existing methods. In addition, a novel method that utilizes unidirectional sparsified communications is introduced and theoretical convergence analysis is also provided. Namely, we prove R-linear convergence in the expected norm. A thorough empirical evaluation of the methods using Message Passing Interface (MPI) on a High Performance Computing (HPC) cluster is carried out and several useful insights and guidelines on the performance of algorithms and inherent communication-computational trade-offs in a realistic setting are derived.
Operational research capacity building through the Structured Operational Research Training Initiative (SORT-IT) in China: implementation, outcomes and challenges
Authors: Feng Ning , Edwards Jeffrey Karl , Owiti Philip Odhiambo , Zhang Guo-Min , Rueda Vallejo Zulma Vanessa , Hann Katrina , Zhou Shui-Sen , Oo Myo Minn , Geoffroy Elizabeth Marie , Ma Chao , Li Tao , Feng Jun , Zhang Yi , Dong Xiao-Ping
Published: June 2021

Background

Chinese Center for Disease Control and Prevention (China CDC) introduced the Structured Operational Research Training Initiative (SORT IT) into China to build a special capacity and equip public health professionals with an effective tool to support developing countries in strengthening their operational research. The paper aims to investigate and analyze the implementation, outcomes and challenges of the first cycle of SORT IT in China.

Main text

As a result of the successful implementation, SORT IT China, Cycle 1 has demonstrated fruitful outputs as exemplified by the 18-month follow-up to the post-training initiatives of the twelve participants, who all achieved the four milestones required by SORT IT. Eleven of twelve (92%) manuscripts generated that focused on the prevention and control of malaria, influenza, HIV/AIDS, hepatitis B, schistosomiasis, tuberculosis and Japanese encephalitis were published by peer-reviewed international journals with the impact factor ranging from 2.6 to 4.8. The most up-to-date citation count on February 19, 2021 was 53 times out of which 31 times were cited by Science Citation Index papers with 94.827 impact factor in total. Six senior professionals from China CDC also facilitated the whole SORT IT training scheme as co-mentors under the guidance of SORT IT mentors. The twelve participants who gained familiarity with the SORT IT courses and training principles are likely become potential mentors for future SORT IT, but they as the non-first language speakers/users of English also faced the challenge in thoroughly understanding the modules delivered in English and writing English academically to draft the manuscripts.

Conclusion

The outcomes from the first cycle of SORT IT in China have led to studies contributing to narrowing the knowledge gap among numerous public health challenges nationally and internationally. It is believed the researchers who participated will continue to apply the skills learned within their domain and help build the training capacity for future operational research courses both in China and in developing countries with similar needs.

Graphic Abstract
Development of a classification system based on corneal biomechanical properties using artificial intelligence predicting keratoconus severity
Authors: Herber Robert , Pillunat Lutz E. , Raiskup Frederik
Published: June 2021

Background

To investigate machine-learning (ML) algorithms to differentiate corneal biomechanical properties between different topographical stages of keratoconus (KC) by dynamic Scheimpflug tonometry (CST, Corvis ST, Oculus, Wetzlar, Germany). In the following, ML models were used to predict the severity in a training and validation dataset.

Methods

Three hundred and eighteen keratoconic and one hundred sixteen healthy eyes were included in this monocentric and cross-sectional pilot study. Dynamic corneal response (DCR) and corneal thickness related (pachymetric) parameters from CST were chosen by appropriated selection techniques to develop a ML algorithm. The stage of KC was determined by the topographical keratoconus classification system (TKC, Pentacam, Oculus). Patients who were classified as TKC 1, TKC 2 and TKC 3 were assigned to subgroup mild, moderate, and advanced KC. If patients were classified as TKC 1–2, TKC 2–3 or TKC 3–4, they were assigned to subgroups according to the normative range of further corneal indices (index of surface variance, keratoconus index and minimum radius). Patients classified as TKC 4 were not included in this study due to the limited amount of cases. Linear discriminant analysis (LDA) and random forest (RF) algorithms were used to develop the classification models. Data were divided into training (70% of cases) and validation (30% of cases) datasets.

Results

LDA model predicted healthy, mild, moderate, and advanced KC eyes with a sensitivity (Sn)/specificity (Sp) of 82%/97%, 73%/81%, 62%/83% and 68%/95% from a validation dataset, respectively. For the RF model, a Sn/Sp of 91%/94%, 80%/90%, 63%/87%, 72%/95% could be reached for predicting healthy, mild, moderate, and advanced KC eyes, respectively. The overall accuracy of LDA and RF was 71% and 78%, respectively. The accuracy for KC detection including all subgroups of KC severity was 93% in both models.

Conclusion

The RF model showed good accuracy in predicting healthy eyes and various stages of KC. The accuracy was superior with respect to the LDA model. The clinical importance of the models is that the standalone dynamic Scheimpflug tonometry is able to predict the severity of KC without having the keratometric data.

Trial registration

NCT04251143 at Clinicaltrials.gov, registered at 12 March 2018 (Retrospectively registered).
Probiotic-related bacteremia after major hepatectomy for biliary cancer: a report of two cases
Authors: Shimura Mitsuhiro , Mizuma Masamichi , Nakagawa Kei , Aoki Shuichi , Miura Takayuki , Takadate Tatsuyuki , Ariake Kyohei , Maeda Shimpei , Kawaguchi Kei , Masuda Kunihiro , Ishida Masaharu , Ohtsuka Hideo , Morikawa Takanori , Kamei Takashi , Unno Michiaki
Published: June 2021

Background

Probiotics have been reported to be beneficial for the prevention of postoperative complications and are often used during the perioperative period. Among the probiotic-related adverse events, bacteremia is rare. Here, we report two cases of probiotic-related bacteremia after major hepatectomy for biliary cancer.

Case presentation 1

A 74-year-old man was referred to our hospital to be treated for gallbladder cancer. Neoadjuvant chemotherapy, two courses of gemcitabine plus S-1 combination therapy, was administered. Extended right hepatectomy with caudate lobectomy, extrahepatic bile duct resection and biliary reconstruction were performed 3 weeks after chemotherapy. Probiotics, Clostridium butyricum (C. butyricum) MIYAIRI 588, were administered 6 days before surgery and continued after surgery. Sepsis of unknown origin occurred 17 days after surgery and developed into septic shock. C. butyricum was detected in blood cultures at postoperative day 26 and 45. After stopping the probiotic agent, C. butyricum was undetectable in the blood cultures. The patient died due to an uncontrollable sepsis 66 days after surgery.

Case presentation 2

A 63-year-old man with diabetes mellitus whose past history included total colectomy, papillectomy, and Frey’s operation at the age of 19, 34 and 48, respectively, was referred to our hospital to be treated for perihilar cholangiocarcinoma. Extended left hepatectomy with caudate lobectomy, extrahepatic bile duct resection and reconstruction of bile duct were performed. Probiotics were administered during the perioperative period. Combined probiotics that included lactomin, amylolytic bacillus and C. butyricum, were given before surgery. C. butyricum MIYAIRI 588 was given after surgery. Sepsis occurred 16 days after surgery and developed to respiratory failure 8 days later. Blood culture at postoperative day 25 revealed Enterococcus faecalis and C. butyricum. After the probiotics were stopped at postoperative day 27, C. butyricum was not detected in the blood culture. The general condition improved with intensive care. The patient was transferred to another hospital for rehabilitation at postoperative day 156.

Conclusion

It should be noted that the administration of probiotics in severe postoperative complications can lead to probiotic-related bacteremia.
Personality traits in patients with refractory versus non-refractory epilepsy
Authors: Elbeh Khaled A. M. , Elserogy Yasser M. , Hamid Menna F. , Gabra Romany H.
Published: May 2021

Background

Epilepsy has significant effects on the behavior of most people who suffer it. In some cases, the seizure activity itself is manifested as a brief change in behavior that might appear unusual to the casual observer. Evidence also suggests that epilepsy can affect behavior when seizures are not occurring. Descriptions of inter-ictal behavior in people with epilepsy have a long and controversial history. The study aims to assess the personality disorders among epileptic patients and impact of the severity of epilepsy on personality traits. Methods: This study is conducted upon 90 patients presented at outpatient clinic of epilepsy in Assiut University Hospital diagnosed as having epilepsy versus 40 cross-matched healthy controls. Patient group were classified into two groups (refractory versus controlled groups). All patients and control were subjected to (1) detailed medical interview. (2) Assessment of intelligence using The Arabic Version of Wechsler Adult Intelligence Scale. (3) Conventional EEG study. (4) The Arabic Version of The Structured interview for the five-factor model of personality.

Results

A relationship was found between personality traits and the severity of epilepsy. When patients have more severe epilepsy, they often have a high seizure frequency, they use more antiepileptic medications. It is likely that in those patients the need for control is usually high (because seizures mean a loss of control). Regarding the five-factor model of personality which we used to assess the personality traits of our selected studied samples, we found that the five main domains of the scale which are neuroticism, extraversion, openness to experience, agreeableness and conscientiousness differ markedly between the two groups of our patients. We found neuroticism was markedly increased at the refractory epileptic patients than the controlled epileptic ones, while extraversion, openness to experience, agreeableness, and conscientiousness increased at the controlled epileptic patients than the refractory epileptic ones.

Conclusion

Patients with epilepsy have raised scores for several personality traits also those personality traits are different in patients with refractory and controlled epilepsy. Also, those personality traits are different compared with a control group from the general population.
Validity of routine biochemical and ultrasound scores for prediction of hepatic fibrosis and steatosis in NAFLD
Authors: Eletreby Rasha , Abdellatif Zeinab , Gaber Yasmine , Ramadan Ahmed , Ahmad Naglaa , Khattab Hany , Said Mohamed , Saad Yasmin
Published: May 2021

Background

We evaluated the validity of some non-invasive scores and ultrasound findings to predict fibrosis and steatosis in a cohort of NAFLD patients who underwent liver biopsy. Ninety-seven NAFLD patients were enrolled and classified into NASH (66) and simple steatosis groups (31) based on liver biopsy. ROC curves were constructed for Fibrosis-4 index (FIB4), aspartate aminotransferase to platelet ratio index (APRI), and NAFLD fibrosis score (NFS) in fibrosis prediction, also for (hepatic steatosis index; HSI, fatty liver index; FLI) and ultrasonographic subcutaneous and visceral adipose tissue measurements (SAT and VAT) for steatosis prediction.

Results

FIB4 had AUC of 0.6, APRI and NFS at cutoffs of 0.3 and -.2.4 had AUC of 0.64 and 0.63 in detecting the presence of any grade of fibrosis, and of (0.52, 0.55, and 0.58) for significant fibrosis. FIB4 at a cut-off of (0.76) had the highest AUC in detecting any grade of fibrosis in the simple steatosis group (0.81). SAT (at cutoff of 2.1 and 2.5) was superior to VAT. HSI (at cutoff 45.35 and 45.7) was superior to FLI in detecting moderate or marked steatosis.

Conclusion

FIB4 and NFS can be used in screening for silent liver disease with ongoing fibrosis in simple steatosis. They are unsatisfactory predictors for significant fibrosis in NAFLD. SAT is better than VAT in predicting moderate steatosis and is slightly better than biochemical HSI.
Predictors of contrast-induced nephropathy in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention
Authors: Abdel-Ghany Mohamed , Morsy Ghada , Kishk Yehia Taha
Published: June 2021

Background

Contrast-induced nephropathy (CIN) is a serious complication with primary percutaneous coronary intervention (PPCI). We aimed to study the different predictors of CIN and determine the cutoff point of contrast volume (CV)/creatinine clearance (CrCl) and the applicability of CHA2DS2-VASC score in the prediction of CIN after PPCI in ST-elevation myocardial infarction (STEMI) patients. Four hundred patients presented with STEMI and eligible for primary PCI were included in the study. Patients with GFR < 30 ml/min were excluded from the study.

Results

Fifty-four (13.5%) patients who developed CIN who were older (64.20 ± 13.16 vs. 55.80 ± 10.58) had a higher prevalence of diabetes mellitus (DM), hypertension (HTN), and female gender than those without CIN. They also had a higher Killip class and lower hemoglobin (HB) level (P< 0.05) compared to those with no CIN. The incidence of no CIN was (85.8%) in the low-risk Mehran score group and 14.2% in the moderate-risk group, and all patients of high and very high score group developed CIN (P<0.001). Multiple logistic regression showed that old age (OR= 1.06, 95% CI= 1.02–1.11,P< 0.001), female sex (OR= 3.1, 95% CI= 2.65–6.99,P= 0.02), high Mehran score (OR=2.48, 95% CI= 1.98–6.24,P= 0.01), CV/CrCl > 2.8 (odds ratio=1.45, 95% CI= 1.22–2.01,P= 0.03), and CHA2DS2-VASC score > 2 (odds ratio=1.90, 95% CI= 1.76–2.11, P= 0.04) were predictors of CIN.

Conclusions

Old age, female sex, high Mehran score, CHADS2-VASC score > 2, CV/CrCl > 2.8 were predictors of CIN in STEMI patients who underwent PPCI.
Monumental geophysics: J. Clarence Karcher and the reflection method
Authors: Frehner Brian
Published: June 2021

You might miss the monument sitting in front of the Belle Isle Library on the outskirts of Oklahoma City if driving by or walking hurriedly past. In the grass between the library and a sidewalk sits a five-foot-tall granite monument adorned with core samples and inscribed with words and images. If you study it, this is in part what you will read:
Borehole seismic methods for geologic CO2storage monitoring
Authors: White Don , Daley Thomas M. , Paulsson Björn , Harbert William
Published: June 2021

Borehole geophysical methods are a key component of subsurface monitoring of geologic CO2storage sites because boreholes form a locus where geophysical measurements can be compared directly with the controlling geology. Borehole seismic methods, including intrawell, crosswell, and surface-to-borehole acquisition, are useful for site characterization, surface seismic calibration, 2D/3D time-lapse imaging, and microseismic monitoring. Here, we review the most common applications of borehole seismic methods in the context of storage monitoring and consider the role that detailed geophysical simulations can play in answering questions that arise when designing monitoring plans. Case study examples are included from the multitude of CO2monitoring projects that have demonstrated the utility of borehole seismic methods for this purpose over the last 20 years.
Barriers and facilitators to mood and confidence in pregnancy and early parenthood during COVID-19 in the UK: mixed-methods synthesis survey
Authors: Perez Alejandra , Panagiotopoulou Elena , Curtis Peter , Roberts Ruth
Published: June 2021

Background

Parental well-being during pregnancy and early parenthood is critical for child development. Environmental stressors can significantly challenge parental well-being.

Aims

To investigate how COVID-19 and associated restrictions influence mood and parenting confidence of expectant parents and those in early parenthood, identifying barriers and facilitators.

Method

We used a cross-sectional online survey to collect data from 590 expectant parents and parents of infants (564 women) during the most restrictive phase of lockdown in the UK. We included a mixture of forced-choice and open-ended questions pertaining to mood, perceived social support, media use, online interactions and parenting expectations. Quantitative data were analysed with multiple linear regression and proportional odds models; an inductive thematic analysis was used for qualitative data. Quantitative and qualitative data were qualitatively synthesised.

Results

Since COVID-19, expectant parents and parents of new-borns reported a decrease in mood and parenting confidence. Barriers included practical difficulties (finding essentials, reliable health information), social difficulties (loss of physical contact, decreased support) and uncertainty during pregnancy. Facilitators included support from others and, for first-time parents, loss of child care resulting in greater parenting confidence. Although online resources and communication were not preferable to face-to-face interactions, technology was a helpful tool for communicating, getting support, and finding essentials and information during lockdown.

Conclusions

By mid-May 2020, mood and parenting confidence among expectant and parents of new-borns in the UK were significantly reduced. Consideration of barriers and facilitators in healthcare and psychological support provided is likely important for promoting parental mental health and healthy parent–child relationships.
Tyrosine Kinase Inhibitors, Antibody-Drug Conjugates, and Proteolysis-Targeting Chimeras: The Pharmacology of Cutting-Edge Lung Cancer Therapies
Authors: Carlisle Jennifer W. , Harvey R. Donald
Published: June 2021

The number of therapeutic options available for patients with advanced non–small-cell lung cancer has been led by deeper understanding of molecular drivers, immune function, and fundamental biology. In this article, we describe the relevant clinical pharmacologic characteristics of three broad classes of existing and investigational treatments, with a focus on mechanisms of action, adverse event profiles, pharmacokinetic and pharmacodynamic properties, and known and predicted resistance pathways. Specifically, within the kinase inhibitor class, agents directed against the RET, MET, and KRAS pathways are reviewed. Additionally, the first antibody-drug conjugates that target HER2 and HER3 are in trials and will ideally be available for patients soon. Finally, proteolysis-targeting chimeras approach pathway inhibition through enzyme degradation rather than target inhibition and are a promising platform for new agents in non–small-cell lung cancer and across cancer types. Each of these classes requires knowledge of clinical pharmacologic principles in development and use to ensure patient care in clinics and trials is optimized and personalized, including dosing and scheduling strategies, potential drug interactions, use in special populations, and monitoring parameters. Ideally, oncologists will continue to have new agents available across the non–small-cell lung cancer treatment spectrum to offer to a patient group that, until relatively recently, had few options.
Deletion of TRPV3 and CaV3.2 T-type channels in mice undermines fertility and Ca2+ homeostasis in oocytes and eggs
Authors: Mehregan Aujan , Ardestani Goli , Akizawa Hiroki , Carvacho Ingrid , Fissore Rafael
Published: June 2021

Ca2+ influx during oocyte maturation and after sperm entry is necessary to fill the internal Ca2+ stores and for complete egg activation. We knocked out the transient receptor potential vanilloid member 3 (TRPV3) and the T-type channel, CaV3.2, to determine their necessity for maintaining these functions in mammalian oocytes/eggs. Double-knockout (dKO) females were subfertile, their oocytes and eggs showed reduced internal Ca2+ stores, and, following sperm entry or Plcz (also known as Plcz1) cRNA injection, fewer dKO eggs displayed Ca2+ responses compared to wild-type eggs, which were also of lower frequency. These parameters were rescued and/or enhanced by removing extracellular Mg2+, suggesting that the residual Ca2+ influx could be mediated by the TRPM7 channel, consistent with the termination of divalent-cation oscillations in dKO eggs by a TRPM7 inhibitor. In total, we demonstrated that TRPV3 and CaV3.2 mediate the complete filling of the Ca2+ stores in mouse oocytes and eggs. We also showed that they are required for initiating and maintaining regularly spaced-out oscillations, suggesting that Ca2+ influx through PM ion channels dictates the periodicity and persistence of Ca2+ oscillations during mammalian fertilization.
Are individuals consistent? Endocrine reaction norms under different ecological challenges
Authors: Baldan Davide , Negash Mekail , Ouyang Jenny Q.
Published: June 2021

Quantifying organismal capacity for compensatory mechanisms is essential to forecast responses to environmental change. Despite accumulating evidence for individual variation in physiological plasticity, the causes and consequences of this variation remain unclear. An outstanding question is whether individual reaction norms are consistent across different environmental challenges, i.e. whether an individual that is responsive to one environmental variable will be equally responsive to a different environmental variable. Additionally, are these reaction norms themselves consistent over time, i.e. repeatable? Here, we quantified individual baseline glucocorticoid responses in house sparrows, Passer domesticus, to sequential manipulations of temperature, wind speed and food unpredictability that were repeated in discrete blocks of sampling under both control and stressor-exposed conditions. Individuals significantly decreased their baseline corticosterone levels and increased their mass during treatment exposure. This response was consistent across environmental challenge types. There was high repeatability in the intercept and slope of the baseline corticosterone reaction norm between environmental challenges but broad credible intervals in the repeatability of the reaction norm slope, suggesting that although glucocorticoid levels during baseline conditions are repeatable, among-individual variation in the shape of the glucocorticoid response may be higher than within-individual variation. Within-subject variation in baseline corticosterone levels was mainly explained by within-individual variation in body mass during stressor exposure. Despite the high lability in physiological traits, endocrine plasticity is repeatable across environmental challenges and may be able to evolve as a result of genetic accommodation, in which selection acts on genetic variation of reaction norms.
Telomerase activity can mediate the effects of growth on telomeres during post-natal development in a wild bird
Authors: Noguera Jose C. , Velando Alberto
Published: June 2021

In wild animals, telomere attrition during early development has been linked with several fitness disadvantages throughout life. Telomerase enzyme can elongate telomeres, but it is generally assumed that its activity is suppressed in most somatic tissues upon birth. However, recent evidence suggests that this may not be the case for long-lived bird species. We have therefore investigated whether telomerase activity is maintained during the postnatal growth period in a wild yellow-legged gull (Larus michahellis) population. Our results indicate that telomerase activity is not negligible in the blood cells, but activity levels sharply decline from hatching to fledging following a similar pattern to the reduction observed in telomere length. Our results further suggest that the observed variation in telomere length may be the result of a negative effect of fast growth on telomerase activity, thus providing a new mechanism through which growth rates may affect telomere dynamics and potentially life-history trajectories.