bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the CHO surfaceome: Identification of cell surface proteins reveals cell aggregation‐relevant mechanisms
Authors: Klingler Florian , Mathias Sven , Schneider Helga , Buck Theresa , Raab Nadja , Zeh Nikolas , Shieh Yu‐Wei , Pfannstiel Jens , Otte Kerstin
Published: May 2021

Chinese hamster ovary (CHO) suspension cells are the main production hosts for biopharmaceuticals. For the improvement of production processes, it is essential to understand the interaction between CHO cells and their microenvironment. While the cellular membrane is the crucial surface barrier between the inner and outer cell compartments, the subgroup of cell surface proteins (surfaceome) is of particular interest due to its potential to react to external factors and initiate cell communication and interaction pathways. Therefore, the CHO surfaceome was explored for the first time by enriching exposed N‐glycosylated membrane proteins before tandem mass spectrometry (MS/MS) analyses, identifying a total of 449 surface proteins, including 34 proteins specific for production cells. Functional annotation and classification located most proteins to the cell surface belonging mainly to the protein classes of receptors, enzymes, and transporters. In addition, adhesion molecules as cadherins, integrins, Ig superfamily and extracellular matrix (ECM) proteins as collagens, laminins, thrombospondin, fibronectin, and tenascin were significantly enriched, which are involved in mechanisms for the formation of cell junctions, cell–cell and cell–ECM adhesion as focal adhesions. As cell adhesion and aggregation counteracts scalable production of biopharmaceuticals, experimental validation confirmed differential expression of integrin β1 (ITGB1) and β3, CD44, laminin, and fibronectin on the surface of aggregation‐prone CHO production cells. The subsequent modulation of the central interaction protein ITGB1 by small interfering RNA knockdown substantially counteracted cell aggregation pointing toward novel engineering routes for aggregation reduction in biopharmaceutical production cells and exemplifying the potential of the surfaceome for specified engineering strategies.
An integrated numerical visualization teaching approach for an undergraduate course, Flow in Porous Media: An attempt toward sustainable engineering education
Authors: Okere Chinedu J. , Su Guandong , Gu Xun , Han Beiyu , Tan Chengwei
Published: May 2021

The complexities of observing flow phenomena in porous media have made it difficult to teach the course, Flow in Porous Media, to undergraduate students majoring in petroleum engineering. In this study, we propose an integrated numerical visualization teaching (INVT) approach that is based on MATLAB Pdetool, graphical user interface, and Visual Basic Programming. The effectiveness of the INVT method was evaluated in two ways: First, via statistical analyses of the examination grades of two groups (experimental and control groups) of selected undergraduate students from the school of petroleum engineering, after a carefully designed INVT tutorial program was conducted on the experimental group, and finally, by interviewing the selected students to ascertain their psychological wellbeing. The following results were obtained: (1) From the statistical analysis, it was observed that the grade distribution, arithmetic mean, median, and maximum scores of students in the experimental group were relatively higher, suggesting that the INVT approach was effective and suitable for the majority of the students. (2) The interviews revealed that the INVT method provides students with a better classroom experience and help them identify their area of interest. (3) The INVT method will provide other benefits, such as cost‐saving, greener classroom​s, decrease carbon footprint, talent and skill enhancement, and achieve sustainable development goals for education. This paper introduces an effective teaching method for environmental and sustainable energy education. To the best of our knowledge, this is the first time the INVT method is adopted in teaching a petroleum engineering professional course.
Self‐reported and general practitioner recorded indicators of lifetime health up to age 48 according to offender type in the Cambridge Study in Delinquent Development
Authors: Skinner Guy C. M. , Farrington David P.
Published: May 2021

Background

Previous research has suggested that people with a history of offending have worse health compared to non‐offenders, but it is less clear whether all types of offenders are at similar health risks. In a New Zealand birth cohort study, Moffitt evidenced three main offending trajectories—life‐course‐persistent (LCP), adolescence‐limited (AL) and late‐onset (LO) offending, subsequently confirmed in other substantial longitudinal studies.

Aims

Our aim was to explore the relationship between these offending trajectories and both self‐reported (SR) and general practitioner (GP) (primary care) recorded health indicators.

Methods

Self‐reported medical data at age 48 were obtained for 394 men followed since age 8 years in the Cambridge Study in Delinquent Development. In addition, medical records were obtained from GPs for 264 of them. Health indicators from both sources were compared between each of the three established trajectories of offenders across the life course—LCP, AL, LO and the non‐offenders.

Results

LCP offenders were found to have over twice the likelihood of disabling medical conditions according to both self‐report and GP records. They were also more likely to have GP records indicating mental health problems and treatment for them. According to GP records alone, the LO offenders were also more likely to have mental health problems. The health of AL offenders appeared to be no different from that of the crime‐free controls.

Conclusions

Our findings add weight to the growing evidence that LCP offending and offending that only occurs relatively late in life are likely to be the indicators of generally unhealthy and disrupted lives. This suggests that if lifestyle is to change for the better, interventions are likely to be needed for health as well as antisocial behaviour.
Current issues on simultaneous TAVR (Transcatheter Aortic Valve Replacement) and EVAR (Endovascular Aneurysm Repair)
Authors: Schizas Nikolaos , Antonopoulos Constantine N. , Patris Vasilios , Lampropoulos Konstantinos , Kratimenos Theodoros , Argiriou Mihalis
Published: May 2021

Simultaneous EVAR and TAVR is technically feasible and is a reliable option in high‐risk patients.
Massive cutaneous complications due to snakebite: A case report and literature review
Authors: Sadeghi Mahdieh , Barazandeh Maryam , Zakariaei Zakaria , Davoodi Lotfollah , Tabaripour Rabeeh , Fakhar Mahdi , Zakariaei Ashkan
Published: May 2021

Wound infections due to snake bites such as cellulitis and necrotizing fasciitis, although not common, are seen in snake bites and if left untreated can cause serious complications.
Impact of ivabradine in decompensated heart failure due to cancer therapy‐related cardiac dysfunction
Authors: Nakano Yusuke , Ando Hirohiko , Suzuki Wataru , Ohashi Hirofumi , Suzuki Yasushi , Takashima Hiroaki , Amano Tetsuya
Published: May 2021

Key Clinical Message

In cases of decompensated heart failure related to cancer therapy‐related cardiac dysfunction, ivabradine administration could lead to an increased stroke volume by reducing the sinus heart rate, resulting in favorable hemodynamics. Assessment of the overlap between the E‐ and A‐waves facilitates understanding the effects of ivabradine in such cases.
Carbon monoxide poisoning during pregnancy treated with hyperbaric oxygen
Authors: Kosaki Yoshinori , Maeyama Hiroki , Nojima Tsuyoshi , Obara Takafumi , Nakao Atsunori , Naito Hiromichi
Published: May 2021

Acute carbon monoxide (CO) intoxication during pregnancy causes fetal death and teratogenic effects. Hyperbaric oxygen (HBO2) therapy has the potential to improve them. HBO2 therapy should be considered to treat CO intoxication during pregnancy.
Vasa praevia with meandering fetal vessels despite placental and umbilical cord insertion on the same side of the uterine wall: A case report
Authors: Horiuchi Tatsuro , Sato Hiroshi , Matsui Katsunori , Ikeda Makiko , Morishita Hajime , Hirose Masaya
Published: May 2021

Vasa praevia with meandering fetal vessels is extremely rare, and it is difficult to diagnose this prenatally. When cesarean section is performed, a change in the site of uterine incision may be required for a safe delivery.
Co‐infection by Cryptococcus neoformans fungaemia and non‐tuberculous mycobacteria with Pneumocystis jiroveci pneumonia in a newly diagnosed HIV‐infected patient
Authors: Subahi Eihab A. , Aljafar Mohamad S. , Barjas Haidar H. , Abdelrazek Mohamed , Rasoul Fatima A.
Published: May 2021

Opportunistic infections are common in human immunodeficiency virus (HIV)‐infected patients. Co‐infections with Cryptococcus neoformans and Mycobacterium species together with Pneumocystis jiroveci pneumonia (PCP) are rare and typically occur in immunocompromised individuals, particularly acquired immunodeficiency syndrome patients.
Energie‐ und Ressourceneinsparung durch Innovative und CFD‐basierte Auslegung von Flüssig/Flüssig‐Schwerkraftabscheidern
Authors: Steinhoff Jan , Charlafti Evgenia , Leleu David , Reinecke Laura , Franken Heinz , Becker Karsten , Kalem Murat , Sixt Maximilian , Braß Manuel , Borchardt Daniel , Bäcker Werner , Wegener Mirco , Maaß Sebastian , Weber Manfred , Acher Thomas , Matten Christian , Pfennig Andreas , Kraume Matthias , Bart Hans‐Jörg
Published: May 2021

Computational‐Fluid‐Dynamics (CFD)‐Simulationen in Kombination mit Tropfenpopulationsbilanzen führen zu einem praxisgerechten Standard, um auf Basis verfügbarer Prozessdaten den Strömungsverlauf – und damit die Verweilzeitverteilung – in liegenden Abscheidern beliebiger Größe zu berechnen. Durch Implementierung des Tropfenverhaltens wird auch die Berechnung eines tropfenspezifischen Abscheider‐Wirkungsgrades ermöglicht. Die Methodenentwicklung erfolgte mit baugleichen Anlagen an drei verschiedenen Standorten. Die darauf beruhenden CFD‐Simulationen wurden erfolgreich mit experimentellen Daten der beteiligten Industriepartner validiert.
Columnar Liquid Crystalline Corannulenes: Synthesis, Assembly and Charge‐Carrier Transport Properties
Authors: Li Yang , Wang Zunzhi , Li Mengwei , Chen Feiyi , Zhao Yang , Wang Qi , Lu Fanli , Liu Yi , Ren Xiang‐Kui , Chen Long
Published: May 2021

Main observation and conclusion

Two discotic liquid crystalline (LC) molecules consisting of a bowl‐shaped corannulene core and five‐fold photoactive azobenzene branches with different paraffinic side chains were developed. Their self‐assembly, photo‐responsive behavior and charge‐carrier transport properties were investigated in detail. A wider mesophase temperature range was achieved when utilizing longer and furcal flexible side chain substitution. 2D XRD measurements revealed the π‐packed corannulene‐centered 1b (i.e., with furcal side alkoxyl chains) exhibited helical columnar LC phase. This packing structure also led to a higher hole charge carrier mobility of 7.07 x 10–2 cm2·V–1·s–1 compared to that of the counterpart 1a with linear side chain substitutions.
A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate‐resistant prostate cancer
Authors: George Daniel J. , Halabi Susan , Heath Elisabeth I. , Sartor A. Oliver , Sonpavde Guru P. , Das Devika , Bitting Rhonda L. , Berry William , Healy Patrick , Anand Monika , Winters Carol , Riggan Colleen , Kephart Julie , Wilder Rhonda , Shobe Kellie , Rasmussen Julia , Milowsky Matthew I. , Fleming Mark T. , Bearden James , Goodman Michael , Zhang Tian , Harrison Michael R. , McNamara Megan , Zhang Dadong , LaCroix Bonnie L. , Kittles Rick A. , Patierno Brendon M. , Sibley Alexander B. , Patierno Steven R. , Owzar Kouros , Hyslop Terry , Freedman Jennifer A. , Armstrong Andrew J.
Published: May 2021

Background

Retrospective analyses of randomized trials suggest that Black men with metastatic castration‐resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race.

Methods

This race‐stratified, multicenter study estimated radiographic progression‐free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate‐specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome‐wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self‐identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients.

Results

The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men.

Conclusions

Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side‐effect rates than White men. This exploratory genome‐wide analysis of TTP identified a possible candidate marker of ancestry‐dependent treatment outcomes.
Sexually dimorphic perineuronal nets in the rodent and primate reproductive circuit
Authors: Ciccarelli Alessandro , Weijers Dilys , Kwan William , Warner Claire , Bourne James , Gross Cornelius T.
Published: May 2021

Perineuronal nets are extracellular glycoprotein structures that have been found on some neurons in the central nervous system and that have been shown to regulate their structural plasticity. Until now work on perineuronal nets has been focused on their role in cortical structures where they are selectively expressed on parvalbumin‐positive neurons and are reported to restrict the experience‐dependent plasticity of inhibitory afferents. Here, we examined the expression of perineuronal nets subcortically, showing that they are expressed in several discrete structures, including nuclei that comprise the brain network controlling reproductive behaviors (e.g., mounting, lordosis, aggression, and social defense). In particular, perineuronal nets were found in the posterior dorsal division of the medial amygdala, the medial preoptic nucleus, the posterior medial bed nucleus of the stria terminalis, the ventrolateral ventromedial hypothalamus and adjacent tuberal nucleus, and the ventral premammillary nucleus in both the mouse and primate brain. Comparison of perineuronal nets in male and female mice revealed a significant sexually dimorphic expression, with expression found prominently on estrogen receptor expressing neurons in the medial amygdala. These findings suggest that perineuronal nets may be involved in regulating neural plasticity in the mammalian reproductive system.
Primary squamous cell carcinoma, breast: A challenging diagnosis
Authors: Goel Divya , Rana Chanchal , Babu Suresh , Ramakant Pooja
Published: May 2021

Background

Primary squamous cell carcinoma of the breast is an extremely rare malignancy constituting less than 0.1% of all breast cancers with very few cases reported in literature. It is an aggressive, triple‐hormone negative tumor, and its appropriate management is still debated. It is diagnostically challenging on both histopathology as well as radiology. Different diagnostic criteria are established for its definite diagnosis. As squamous cells are not found normally in the breast, various theories have been proposed regarding its origin. But the exact pathogenesis is still unclear. We report one such case encountered.

Case

A 54‐year‐old female presented with gradually progressive painless lump in the right breast for 3 months with no other clinical features. There was neither any history of chronic or malignant disease in the patient nor in her family. On clinical examination, there was well‐defined, firm and nontender swelling in upper inner quadrant measuring 3 × 2 cm with overlying skin being normal. There was no swelling in the contralateral breast as well as in the bilateral axillary region. A suspicion of malignancy was raised on initial core needle biopsy and, on repeat biopsy, was diagnosed as metaplastic carcinoma with squamous differentiation. Later, on final resection, specimen was reported as primary squamous cell carcinoma of the breast without any nodal metastasis. All the metastatic causes were ruled out through proper clinical, radiological, and histopathological correlation.

Conclusion

Primary squamous cell carcinoma of the breast is an aggressive tumor with its treatment protocol being still unclear, owing to its rarity. It is important to rule out the metastatic causes. It is relatively resistant to conventional chemotherapy, and its prognosis is also unpredictable. Hence, this requires further studies in terms of management and prognosis.
Learners’ views of literature in EFL education from curricular and assessment perspectives
Authors: Tsang Art , Paran Amos
Published: May 2021

Literature has been gaining growing attention in second language (L2)/foreign language (FL) education globally. In a number of places such as Hong Kong, literature has recently been given greater emphasis in the L2/FL curricula. This article reports part of a large‐scale study examining learners’ views of two English‐as‐a‐foreign‐language (EFL) modules on literary genres recently incorporated in the EFL curriculum, namely short stories (ShS) and poems and songs (P&S), from curricular and assessment perspectives. A total of 1190 secondary school students in Hong Kong completed a questionnaire, yielding quantitative and qualitative data; the 2347 comments collected explained their perceptions from multiple angles. Overall, the participants held positive views of the ShS module being incorporated into the curriculum, but only neutral views of the P&S module. When considering assessment, the respondents demonstrated ambivalence towards the modules; they were mostly against these genres being examined and if unexamined, they were generally not interested in studying them.
A lightweight authentication protocol for IoT‐based cloud environment
Authors: Zargar Sadra , Shahidinejad Ali , Ghobaei‐Arani Mostafa
Published: May 2021

With the ever‐growing use of active internet devices, the Internet of Things (IoT) has achieved vast popularity at present. Authentication technology is essential for the success of integrating IoT and cloud computing. Recently, the adversary capabilities are enhanced, and the current authentication techniques are vulnerable in plenty of possible network attacks. This paper presents a secure and lightweight authentication protocol for IoT‐based cloud environment. The proposed scheme can withstand various attacks and provide secure mutual authentication and anonymity by utilizing secret parameters and biometric. Lightweight crypto modules are adopted to pursue the best energy efficiency. The AVISPA tool is used to evaluate the protocol's performance. The obtained results indicate that the proposed protocol can effectively resist all kinds of known vulnerabilities.
eDNA metabarcoding outperforms traditional fisheries sampling and reveals fine‐scale heterogeneity in a temperate freshwater lake
Authors: Gehri Rebecca R. , Larson Wesley A. , Gruenthal Kristen , Sard Nicholas M. , Shi Yue
Published: May 2021

Understanding biodiversity in aquatic systems is critical to ecological research and conservation efforts, but accurately measuring species richness using traditional methods can be challenging. Environmental DNA (eDNA) metabarcoding, which uses high‐throughput sequencing and universal primers to amplify DNA from multiple species present in an environmental sample, has shown great promise for augmenting results from traditional sampling to characterize fish communities in aquatic systems. Few studies, however, have compared exhaustive traditional sampling with eDNA metabarcoding of corresponding water samples at a small spatial scale. We intensively sampled Boardman Lake (1.4 km2) in Michigan, USA, from May to June in 2019 using gill and fyke nets and paired each net set with lake water samples collected in triplicate. We analyzed water samples using eDNA metabarcoding with 12S and 16S fish‐specific primers and compared estimates of fish diversity among methods. In total, we set 60 nets and analyzed 180 1 L lake water samples. We captured a total of 12 fish species in our traditional gear and detected 40 taxa in the eDNA water samples, which included all the species observed in nets. The 12S and 16S assays detected a comparable number of taxa, but taxonomic resolution varied between the two genes. In our traditional gear, there was a clear difference in the species selectivity between the two net types, and there were several species commonly detected in the eDNA samples that were not captured in nets. Finally, we detected spatial heterogeneity in fish community composition across relatively small scales in Boardman Lake with eDNA metabarcoding, but not with traditional sampling. Our results demonstrated that eDNA metabarcoding was substantially more efficient than traditional gear for estimating community composition, highlighting the utility of eDNA metabarcoding for assessing species diversity and informing management and conservation.
Ubiquitin‐proteasome‐system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF
Authors: Adams Volker , Wunderlich Sebastian , Mangner Norman , Hommel Jennifer , Esefeld Katrin , Gielen Stephan , Halle Martin , Ellingsen Øyvind , Van Craenenbroeck Emeline M. , Wisløff Ulrik , Pieske Burkert , Linke Axel , Winzer Ephraim B.
Published: May 2021

Background

Skeletal muscle (SM) alterations contribute to exercise intolerance in heart failure patients with preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction (LVEF). Protein degradation via the ubiquitin‐proteasome‐system (UPS), nuclear apoptosis, and reduced mitochondrial energy supply is associated with SM weakness in HFrEF. These mechanisms are incompletely studied in HFpEF, and a direct comparison between these groups is missing.

Methods and results

Patients with HFpEF (LVEF ≥ 50%, septal E/e′ > 15 or >8 and NT‐proBNP > 220 pg/mL, n = 20), HFrEF (LVEF ≤ 35%, n = 20) and sedentary control subjects (Con, n = 12) were studied. Inflammatory markers were measured in serum, and markers of the UPS, nuclear apoptosis, and energy metabolism were determined in percutaneous SM biopsies. Both HFpEF and HFrEF showed increased proteolysis (MuRF‐1 protein expression, ubiquitination, and proteasome activity) with proteasome activity significantly related to interleukin‐6. Proteolysis was more pronounced in patients with lower exercise capacity as indicated by peak oxygen uptake in per cent predicted below the median. Markers of apoptosis did not differ between groups. Mitochondrial energy supply was reduced in HFpEF and HFrEF (complex‐I activity: −31% and −53%; malate dehydrogenase activity: −20% and −29%; both P < 0.05 vs. Con). In contrast, short‐term energy supply via creatine kinase was increased in HFpEF but decreased in HFrEF (47% and −45%; P < 0.05 vs. Con).

Conclusions

Similarly to HFrEF, skeletal muscle in HFpEF is characterized by increased proteolysis linked to systemic inflammation and reduced exercise capacity. Energy metabolism is disturbed in both groups; however, its regulation seems to be severity‐dependent.
Rhodium(III)‐Catalyzed Dehydrogenative Annulation of 2‐Arylindazoles with Cyclic Enones
Authors: Chary Devulapally Yogananda , Ittamalla Chaitanya , Balasubramanian S. , Venkata Subba Reddy Basireddy
Published: May 2021

An oxidative annulation of 2‐arylindazoles with cyclic enoneshas was developed using Rh(III)/Cu(OAc)2 catalytic system for the first time to produce 3,4‐dihydroindazolo[2,3‐f]phenanthridin‐1(2H)‐one derivatives in good yields with high selectivity. When AgSbF6 was used instead of Cu(OAc)2, the corresponding uncyclized products, 3‐(2‐(2H‐indazol‐2‐yl)phenyl)cyclohexan‐1‐one scaffolds were formed exclusively. The reaction proceeds through a sequential conjugate addition of ortho‐C–H bond of aryl group followed by an oxidative annulation of indazole ring to generate fused polycyclic scaffolds.
Interpretable machine learning methods for in vitro pharmaceutical formulation development
Authors: Ye Zhuyifan , Yang Wenmian , Yang Yilong , Ouyang Defang
Published: May 2021

Background

Machine learning has become an alternative approach for pharmaceutical formulation development. However, many machine learning applications in pharmaceutics only focus on model performance rather than model interpretability.

Aim

This study aims to propose an attention‐based deep neural network (DNN) for pharmaceutical formulation development.

Methods

An attention‐based DNN, AttPharm, was proposed. AttPharm separately handled feature values and feature physical meaning by representation learning to successfully apply the attention mechanism to the pharmaceutical tabular data. Furthermore, the distributions of the attention weights were computed using AttPharm. Two post hoc methods, local interpretable model‐agnostic explanation (LIME) and TreeSHAP, were utilized to obtain the post hoc model interpretability for lightGBM.

Results

The results demonstrated that AttPharm significantly improved the model performance of plain neural networks on a pharmaceutical cyclodextrin dataset because the attention mechanism could extract related features and find minute variation. Notably, the attention weights were analyzed, which illustrated global and local feature‐level and sample‐level model interpretability, thus providing insights for formulation design. Comparing with post hoc methods, AttPharm can be used without the concern of the faithfulness of interpretability.

Conclusion

This is the first step in applying the attention‐based DNN to pharmaceutical formulation development. Considering the importance of model interpretability, the proposed approach may have a wide range of applications in pharmaceutics.
Mediterranean diet adherence and dietary calcium intake in a group of pregnant women: Results of an Italian survey
Authors: Quattrini Sara , Pampaloni Barbara , Cianferotti Luisella , Fossi Caterina , Ottanelli Silva , Gronchi Giorgio , Duradoni Mirko , Di Tommaso Mariarosaria , Dubini Valeria , Brandi Maria Luisa
Published: May 2021

Pregnancy is a delicate phase in woman's life that could become a risk factor for osteoporosis in pregnant women who do not meet recommended nutrient standards, especially for calcium and vitamin D. Mediterranean diet (MD) has been demonstrated to be beneficial for adequate nutrient intake. This article aims to evaluate the MD adherence and dietary calcium intake in a group of pregnant Italian women and to investigate how these are linked to each other and to fast glycemia at first trimester of pregnancy. Two hundred and seventy‐nine pregnant women were recruited at the gynecology units of two hospitals in Florence. Socio‐demographic, clinical information, and results of the first trimester blood sample analysis were collected. Two questionnaires, validated for evaluation of MD adherence and calcium intake, were administered to the pregnant women. Approximately 60% of the women had a high level of MD adherence, with a mean dietary calcium intake of 870.3 ± 335.3. In women with higher MD adherence level, fast glycemia resulted lower. Calcium intake was lower than Population Rate Intake for the Italian population (1,200 mg/daily) and was positively correlated to MD adherence score. The MD proved to be nutritious, as it was related to a higher calcium intake in this group of Italian women.
Statistical evaluation of main extraction parameters in twenty plant extracts for obtaining their optimum total phenolic content and its relation to antioxidant and antibacterial activities
Authors: Kadir Dler H.
Published: May 2021

The main extraction parameters were statistically evaluated for 20 medicinal plants to obtain the optimum conditions for maximum extraction of total phenolic content (TPC) in each plant. Among various extraction parameters, pH, temperature, and concentration at different levels were studied. The results were analyzed using the analysis of variance to achieve the optimum conditions of phenolic extraction for all plants. Also, investigation of the optimum antioxidant (AnOX) activities using DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) method and antibacterial potential against common pathogenic bacteria of Staphylococcus aureus, Escherichia coli, Pseudomonas spp., and Candida spp. through disk diffusion method for the extract of all plants under the optimum total phenolic concentration of each plant extract confirmed a direct relation among bioactivity and TPC.
Increased segregation of structural brain networks underpins enhanced broad cognitive abilities of cognitive training
Authors: Chen Quanjing , Baran Timothy M. , Turnbull Adam , Zhang Zhengwu , Rebok George W. , Lin Feng Vankee
Published: May 2021

A major challenge in the cognitive training field is inducing broad, far‐transfer training effects. Thus far, little is known about the neural mechanisms underlying broad training effects. Here, we tested a set of competitive hypotheses regarding the role of brain integration versus segregation underlying the broad training effect. We retrospectively analyzed data from a randomized controlled trial comparing neurocognitive effects of vision‐based speed of processing training (VSOP) and an active control consisting of mental leisure activities (MLA) in older adults with MCI. We classified a subset of participants in the VSOP as learners, who showed improvement in executive function and episodic memory. The other participants in the VSOP (i.e., VSOP non‐learners) and a subset of participants in the MLA (i.e., MLA non‐learners) served as controls. Structural brain networks were constructed from diffusion tensor imaging. Clustering coefficients (CCs) and characteristic path lengths were computed as measures of segregation and integration, respectively. Learners showed significantly greater global CCs after intervention than controls. Nodal CCs were selectively enhanced in cingulate cortex, parietal regions, striatum, and thalamus. Among VSOP learners, those with more severe baseline neurodegeneration had greater improvement in segregation after training. Our findings suggest broad training effects are related to enhanced segregation in selective brain networks, providing insight into cognitive training related neuroplasticity.
Bile Salt and FGF19 Signaling in the Early Phase of Human Liver Regeneration
Authors: Koelfat Kiran V.K. , van Mierlo Kim M.C. , Lodewick Toine M. , Bloemen Johanne G. , van der Kroft Gregory , Amygdalos Iakovos , Neumann Ulf P. , Dejong Cornelis H.C. , Jansen Peter L.M. , Olde Damink Steven W.M. , Schaap Frank G.
Published: May 2021

The involvement of bile salt–fibroblast growth factor 19 (FGF19) signaling in human liver regeneration (LR) is not well studied. Therefore, we studied aspects of bile salt–FGF19 signaling shortly after liver resection in patients. We compared plasma bile salt and FGF19 levels in arterial, portal and hepatic venous blood, calculated venous‐arterial differences (ΔVA), and determined hepatic transcript levels on two intra‐operative time points: before (< 1 hour) and immediately after (> 2‐3 hours) liver resection (i.e., following surgery). Postoperative bile salt and FGF19 levels were assessed on days 1, 2, and 3. LR was studied by computed tomography (CT)–liver volumetry. Following surgery, the liver, arterial, and portal bile salt levels were elevated (P < 0.05). Furthermore, an increased amount of bile salts was released in portal blood and extracted by the remnant liver (P < 0.05). Postoperatively, bile salt levels were elevated from day 1 onward (P < 0.001). For FGF19, intra‐operative or postoperative changes of ΔVA or plasma levels were not observed. The bile salt–homeostatic regulator farnesoid X receptor (FXR) was markedly up‐regulated following surgery (P < 0.001). Cell‐cycle re‐entry priming factors (interleukin 6 [IL‐6], signal transducer and activator of transcription 3 [STAT3], and cJUN) were up‐regulated following surgery and were positively correlated with FXR expression (P < 0.05). Postoperative hyperbilirubinemia was preceded by postsurgery low FXR and high Na+/Taurocholate cotransporting polypeptide (NTCP) expression in the remnant liver coupled with higher liver bile salt content (P < 0.05). Finally, bile salt levels on postoperative day 1 were an independent predictor of LR (P < 0.05). Conclusion: Systemic, portal, and liver bile salt levels are rapidly elevated after liver resection. Postoperative bile salts were positively associated with liver volume gain. In the studied time frame, FGF19 levels remained unaltered, suggesting that FGF19 plays a minor role in human LR. These findings indicate a more relevant role of bile salts in human LR.
In Vitro Model for a Drug Assessment of Cytochrome P450 Family 3 Subfamily A Member 4 Substrates Using Human Induced Pluripotent Stem Cells and Genome Editing Technology
Authors: Deguchi Sayaka , Shintani Tomohiro , Harada Kazuo , Okamoto Toru , Takemura Akinori , Hirata Kazumasa , Ito Kousei , Takayama Kazuo , Mizuguchi Hiroyuki
Published: May 2021

In drug development, a system for predicting drug metabolism and drug‐induced toxicity is necessary to ensure drug safety. Cytochrome P450 family 3 subfamily A member 4 (CYP3A4) is an important drug‐metabolizing enzyme expressed in the liver and small intestine, and predicting CYP3A4‐mediated drug metabolism and drug‐induced toxicity is essential. We previously developed procedures to differentiate human induced pluripotent stem (iPS) cells into hepatocyte‐like cells (HLCs) or intestinal epithelial‐like cells (IECs) with a fetal phenotype as well as a highly efficient genome editing technology that could enhance the homologous recombination efficiency at any locus, including CYP3A4. By using human iPS cells and our genome editing technology, we generated CYP3A4‐knockout (KO) iPS cell‐derived HLCs and IECs for the evaluation of CYP3A4‐mediated drug metabolism and drug‐induced toxicity. CYP3A4 deficiency did not affect pluripotency and hepatic and intestinal differentiation capacities, and CYP3A4 activity was entirely eradicated by CYP3A4 KO. Off‐target effects (e.g., inhibition of bile acid excretion) were hardly observed in CYP3A4‐KO cells but were observed in CYP3A4 inhibitor‐treated (e.g., ketoconazole) cells. To evaluate whether drug‐induced hepatotoxicity and enterotoxicity could be predicted using our model, we exposed CYP3A4‐KO HLCs and IECs to acetaminophen, amiodarone, desipramine, leflunomide, tacrine, and tolcapone and confirmed that these cells could predict CYP3A4‐mediated toxicity. Finally, we examined whether the therapeutic effects of an anti‐hepatitis C virus (HCV) drug metabolized by CYP3A4 would be predicted using our model. CYP3A4‐KO HLCs were treated with asunaprevir (antiviral drug metabolized by CYP3A4) after HCV infection, and the anti‐viral effect was indeed strengthened by CYP3A4 KO. Conclusion: We succeeded in generating a novel evaluation system for prediction of CYP3A4‐mediated drug metabolism and drug‐induced toxicity.
The impact of socioeconomic status on stage at presentation, receipt of diagnostic imaging, receipt of treatment and overall survival in colorectal cancer patients
Authors: Shah Rajan , Chan Kelvin K. W.
Published: May 2021

Socioeconomic factors influence patterns of care in colorectal cancer. Our study investigates the impact of socioeconomic status (SES) on stage at presentation, receipt of diagnostic imaging, receipt of treatment and overall survival (OS) in a universal healthcare system. The Ontario Cancer Registry (OCR) was accessed to identify a cohort of patients diagnosed with colorectal adenocarcinoma from 2007 to 2016 in Ontario, Canada. SES was measured using median neighborhood income divided into quintiles (Q1‐Q5; Q1 = lowest income). Logistic regression analyses were used to evaluate stage, imaging and treatment. Cox proportional hazards models were used to evaluate OS. All endpoints were adjusted for demographics and comorbidities with OS models also adjusting for stage, imaging and treatment. In total, 39 802 colon and 13 164 rectal patients were identified. Lower SES was associated with advanced stage at presentation in both cohorts (Q1 vs Q5: Colon odds ratio [OR] = 1.08,P = .046, rectal OR = 1.25,P < .0001). Lower SES colon patients were less likely to receive adjuvant oxaliplatin (Q1 vs Q5: OR = 0.78,P < .001) and all palliative chemotherapies studied including oxaliplatin (Q1 vs Q5: OR = 0.60,P < 0.0001), irinotecan (Q1 vs Q5: OR = 0.65,P < .0001), bevacizumab (Q1 vs Q5: OR = 0.70,P < .001), cetuximab (Q1 vs Q5: OR = 0.40,P = .0053) and panitumumab (Q1 vs Q5: OR = 0.54,P = .0036). In rectal patients, lower SES was associated with decreased receipt of rectal cancer resection for stages I‐III (Q1 vs Q5: OR = 0.78,P < .001), adjuvant oxaliplatin (Q1 vs Q5: OR = 0.72,P = .0020) and palliative chemotherapies including oxaliplatin (Q1 vs Q5: OR = 0.59,P < .001), irinotecan (Q1 vs Q5: OR = 0.53,P < .001) and bevacizumab (Q1 vs Q5: OR = 0.71,P = .046). All survival models identified poorer OS for lower SES patients (total colorectal; Q1 vs Q5: Hazard ratio [HR] = 1.25,P < .0001). These findings suggest disparities persist even within universal healthcare.
Uncovering generative mechanisms of information use for project monitoring in humanitarian health management information systems
Authors: Huser David , Bon Anna , Anifalaje Adebusoye
Published: May 2021

Humanitarian medical organizations rely on information on and from the ground to evaluate their effectiveness and accountability. Related digitalization efforts within health information systems assume an instrumental rationality in the use of data. However, previous research identified a multitude of factors influencing actual information use for evidence‐based decision‐making for healthcare delivery. This case study, anchored by critical realism philosophy, unpacks these nuances against the backdrop of a globally operating organization (Médecins Sans Frontières). It aims to highlight the contextual conditions and structures that enact the contingent mechanisms at work in project monitoring within humanitarian health management information systems. By applying an affordance‐based causal analysis, three mechanisms are identified: first, an analytics service provides templated analysis modalities resulting in user–producer–provider relationships; second, the rationalization and synchronization of content and software artifacts gives rise to the standardization strategy of flexible generification; third, the study uncovers the potential for increased internal social discourse and advocacy through collaborative and mobile data analysis. This paper proposes that mechanism‐based explanations can be useful for theory‐building in information systems research as well as for providing insights to practitioners in the humanitarian health sector.
Cognitive vulnerabilities to anxiety symptoms among Chinese adolescents: A 3‐year longitudinal study
Authors: Ho Samuel MY , Zhang Qiaochu , Lai Yihuan , Dai Darren W.T.
Published: May 2021

Objective

This study established cognitive vulnerability of anxiety symptoms among high school students.

Method

A total of 72 grade 9–11 students completed measures on levels of anxiety sensitivity (AS), selective attentional processing, and anxiety symptoms annually between 2016 and 2018.

Results

Latent class growth analysis (unconditional model) showed a four‐class model: High (stable) (6.94%), low (stable) (11.11%), medium (decreasing) (61.11%), and medium (increasing) (20.83%). The conditioned model controlling for the physical‐concerns dimension of AS and negative attentional bias demonstrated that a two‐class model consisted of a low anxiety class (n = 59, 81.9%) and a high anxiety class (n = 13, 18.1%) provided the best fit for the data. Negative attentional bias is a significant factor related to the development of anxiety trajectories.

Conclusion

Attentional bias modification to disengage from negative stimuli may serve as a potential target of intervention to reduce chronic anxiety among high school students.
Mouse models of sarcopenia: classification and evaluation
Authors: Xie Wen‐qing , He Miao , Yu Deng‐jie , Wu Yu‐xiang , Wang Xiu‐hua , Lv Shan , Xiao Wen‐feng , Li Yu‐sheng
Published: May 2021

Sarcopenia is a progressive and widespread skeletal muscle disease that is related to an increased possibility of adverse consequences such as falls, fractures, physical disabilities and death, and its risk increases with age. With the deepening of the understanding of sarcopenia, the disease has become a major clinical disease of the elderly and a key challenge of healthy ageing. However, the exact molecular mechanism of this disease is still unclear, and the selection of treatment strategies and the evaluation of its effect are not the same. Most importantly, the early symptoms of this disease are not obvious and are easy to ignore. In addition, the clinical manifestations of each patient are not exactly the same, which makes it difficult to effectively study the progression of sarcopenia. Therefore, it is necessary to develop and use animal models to understand the pathophysiology of sarcopenia and develop therapeutic strategies. This paper reviews the mouse models that can be used in the study of sarcopenia, including ageing models, genetically engineered models, hindlimb suspension models, chemical induction models, denervation models, and immobilization models; analyses their advantages and disadvantages and application scope; and finally summarizes the evaluation of sarcopenia in mouse models.
Pneumothorax presenting as epigastric pain
Authors: Mizumoto Junki
Published: May 2021

A male patient who smoked heavily complained of severe epigastric pain. He also had mild chest pain for the last 4 weeks. Imaging tests revealed pneumothorax secondary to cystic changes probably as a result of chronic obstructive pulmonary disease. Pneumothorax, particularly slowly progressive one, may present as abdominal pain. In addition to cardiovascular and gastrointestinal diseases, pneumothorax should be considered as a differentiasl diagnosis of epigastric pain with preceding pain or other symptoms in a heavy smoker.
Potential gains: Comparison of a mono‐isocentric three‐dimensional conformal radiotherapy (3D‐CRT) planning technique to hybrid intensity‐modulated radiotherapy (hIMRT) to the whole breast and supraclavicular fossa (SCF) region
Authors: Ambrose Leigh , Stanton Cameron , Lewis Lorraine , Lamoury Gillian , Morgia Marita , Carroll Susan , Bromley Regina , Atyeo John
Published: May 2021

Introduction

Until late 2018, standard of practice at the Northern Sydney Cancer Centre (NSCC) for breast and nodal treatment was a conformal mono‐isocentric technique. A planning study comparing an existing mono‐isocentric three‐dimensional conformal radiotherapy (3D‐CRT) planning technique to a hybrid intensity‐modulated radiotherapy (hIMRT) approach for the whole breast and supraclavicular fossa (SCF) region was undertaken with the aim to improve plan quality by improving dose conformity/homogeneity across target volumes and reducing hotspots outside the target.

Methods

A cohort of 17 patients was retrospectively planned using the proposed hIMRT technique, keeping the same planning constraints as the original treated breast and SCF 3D‐CRT plan and normalising the 3D‐CRT plans to achieve minimum breast/SCF target coverage to compare organs at risk (OARs). Normal tissue index (NTI) and homogeneity index (HI) were compared for plan quality as well as for evaluating OARs.

Results

The hIMRT technique showed statistically significant improvements in NTI and HI, as well as improvement in maximum brachial plexus and thyroid doses. There was a negligible increase in maximum oesophagus dose which could be improved if used in optimisation. Other OAR doses in the irradiated region were comparable to the 3D‐CRT plans, however maximum doses were reduced overall.

Conclusion

The hIMRT planning technique maintained clinically acceptable doses to OARs and reduced normal tissue dose while maintaining equivalent dose coverage to breast and SCF planning target volumes with improved conformity and homogeneity. The reduction in maximum doses promotes a favourable toxicity profile, with potential benefit of improved long‐term cosmesis.
Ablation therapy for ventricular arrhythmias in patients with LVAD: Multiple faces of an electrophysiological challenge
Authors: Sisti Nicolò , Santoro Amato , Carreras Giovanni , Valente Serafina , Donzelli Stefano , Mandoli Giulia Elena , Sciaccaluga Carlotta , Cameli Matteo
Published: May 2021

Left ventricular assist device implantation is a recognized treatment option for patients with advanced heart failure refractory to medical therapy and can be used both as bridge to transplantation and as destination therapy. The risk of ventricular arrhythmias is common after left ventricular assist device implantation and is influenced by pre‐, peri and post‐operative determinants. The management of ventricular arrhythmias can be a challenge when they become refractory to medication or to device therapy and their impact on prognosis can be detrimental despite the mechanical support. In this setting, catheter ablation is being increasingly recognized as a feasible option for patients in which standard therapeutic strategies fail, but also with preventive purpose. Catheter ablation is being increasingly considered for the management of ventricular arrhythmias in patients with left ventricular assist device despite complex clinical and technical peculiarities due to the characteristics of the mechanical support. Much conflicting data exist regarding the predictors of success of the procedure and the rate of recurrence. In this review we discuss the latest evidences regarding catheter ablation of ventricular arrhythmias in this subset of patients, focusing on clinical characteristics, arrhythmia etiology, technical aspects and postprocedural features which must be considered by the electrophysiologist.
High‐level production of microbial prodigiosin: A review
Authors: Han Rui , Xiang Roujin , Li Jinglin , Wang Fengqing , Wang Chuan
Published: May 2021

Prodigiosin is a natural red pigment derived primarily from secondary metabolites of microorganisms, especiallySerratia marcescens. It can also be chemically synthesized. Prodigiosin has been proven to have antitumor, antibacterial, antimalaria, anti‐insect, antialgae, and immunosuppressive activities, and is gaining increasing important in the global market because of its great potential application value in clinical medicine development, environmental treatment, preparation of food additives, and so on. Due to the low efficiency of prodigiosin chemical synthesis, high‐level prodigiosin of production by microorganisms are necessary for prodigiosin applications. In this paper, the production of prodigiosin by microorganism in recent decades is reviewed. The methods and strategies for increasing the yield of prodigiosin are discussed from the aspects of medium composition, additives, factors affecting production conditions, strain modification, and fermentation methods.