bluuebunny/crossref_metadata_2025 huggingface dataset:
Translating In Vitro Acrolein‐Trapping Capacities of Tea Polyphenol and Soy Genistein to In Vivo Situation is Mediated by the Bioavailability and Biotransformation of Individual Polyphenols
Authors: Huang Qiju , Zhu Yingdong , Lv Lishuang , Sang Shengmin
Published: October 2019

Scope

Acrolein (ACR) is a highly toxic unsaturated aldehyde. Humans are both endogenously and exogenously exposed to ACR. Long‐term exposure to ACR leads to various chronic diseases. Dietary polyphenols have been reported to be able to attenuate ACR‐induced toxicity in vitro via formation of ACR‐polyphenol conjugates. However, whether in vitro ACR‐trapping abilities of polyphenols can be maintained under in vivo environments is still unknown.

Methods and results

Two most commonly consumed dietary polyphenols, (−)‐epigallocatechin‐3‐gallate (EGCG) from tea and genistein from soy, are evaluated for their anti‐Acrolein behaviors both in vitro and in mice. Tea EGCG exerts a much higher capacity to capture ACR than soy genistein in vitro. But translation of in vitro anti‐ACR activity into in vivo is mainly mediated by bioavailability and biotransformation of individual polyphenols. It is found that 1) both absorbed EGCG and genistein can trap endogenous ACR by forming mono‐ACR adducts and eventually be excreted into mouse urine; 2) both absorbed EGCG and genistein can produce active metabolites, methyl‐EGCG (MeEGCG) and orobol, to scavenge endogenous ACR; 3) both MeEGCG and non‐absorbed EGCG show ability to trap ACR in the gut; 4) considerable amounts of microbial metabolites of genistein display enhanced anti‐ACR capacity both in the body and in the gut, compared to genistein; and 5) biotransformation of genistein is able to boost its in vivo anti‐ACR capacity, compared to EGCG.

Conclusion

The findings demonstrate that in vivo anti‐ACR ability of dietary polyphenols cannot be reflected solely based on their in vitro ability. The bioavailability and biotransformation of individual polyphenols, and especially the gut microbiome, contribute to in vivo anti‐ACR ability of dietary polyphenols.
The 1H and 13C NMR chemical shifts of Strychnos alkaloids revisited at the DFT level
Authors: Semenov Valentin A. , Samultsev Dmitry O. , Krivdin Leonid B.
Published: October 2019

The density functional theory calculation of 1H and 13C NMR chemical shifts in a series of ten 10 classically known Strychnos alkaloids with a strychnine skeleton was performed at the PBE0/pcSseg‐2//pcseg‐2 level. It was found that calculated 1H and 13C NMR chemical shifts provided a markedly good correlation with experiment characterized by a mean absolute error of 0.08 ppm in the range of 7 ppm for protons and 1.67 ppm in the range of 150 ppm for carbons, so that a mean absolute percentage error was as small as ~1% in both cases.
RF field strength control and an envelope detector
Authors: Lusk Greg , Gullion Terry
Published: October 2019

A brief description of a radio‐frequency (RF) field strength controller is presented along with an experiment to test the long‐term RF field strength stability of a nuclear magnetic resonance (NMR) spectrometer. Active control of RF field strengths may be necessary for quantitative measurements of NMR parameters, especially when experiments require days to run. An envelope detector, easily incorporated in any spectrometer, is also presented. The envelope detector provides an easy way to observe the pulse sequence on an inexpensive oscilloscope and can be useful in troubleshooting.
Age and Growth of Freshwater Drum and Gizzard Shad Occupying Two Reservoir-River Complexes with Different Groundwater Contributions
Authors: Dattilo John , Shoup Daniel E. , Brewer Shannon K.
Published: October 2019

Restoring groundwater flow is a management option that improves water temperature regimes and benefits fishes. Although this strategy applies more readily to river systems, the thermal character of reservoirs is heavily influenced by inflowing rivers. We examined differences in age, structure, and growth of both Freshwater Drum Aplodinotus grunniens and Gizzard Shad Dorosoma cepedianum that occupy catchments with varying groundwater contributions in the south-central United States. Seepage run data indicated that the Kiamichi River was losing surface water to groundwater in summer 2016, whereas groundwater inflows were apparent in the Elk River basin. Summer 2016 data showed that the Elk River had cooler water temperatures than the Kiamichi River and Grand Lake O’ the Cherokees water temperatures were similar to those in the incoming Elk River. We found higher densities of older Freshwater Drum and Gizzard Shad (maximums of 32 and 8 years old, respectively) in samples from the Grand basin than among fish that were sampled from the Kiamichi River basin (21 and 6 years old, respectively). Freshwater Drum grew at similar rates in both basins even though they reached larger maximum lengths in the Grand basin (649 mm TL) than in the Kiamichi River basin (600 mm). The average asymptotic length was greater for the Kiamichi population (L∞ = 613 mm) than for the Grand population (L∞ = 557 mm). Gizzard Shad from the Grand basin were larger than those from the Kiamichi River basin, though the latter population grew faster initially (Brody growth coefficient: K = 0.787 versus K = 0.179, respectively), but they had smaller asymptotic length (L∞ = 206 mm versus L∞ = 343 mm). The role that groundwater plays in temperature regulation in these basins partially explains the observed differences. Our results suggest that the metabolic theory of ecology can be applied to fisheries management at a finer spatial scale.
Incontinence and psychological symptoms in Phelan‐McDermid syndrome
Authors: Hussong Justine , Wagner Catharina , Curfs Leopold , von Gontard Alexander
Published: October 2019

Aims

Phelan‐McDermid syndrome (PMD) is a congenital syndrome caused by a deletion on chromosome 22q13.3. About 600 cases have been identified worldwide. PMD is characterized by neonatal hypotonia, moderate/severe intellectual impairment, impaired expressive language, and typical dysmorphic features. Psychological symptoms as hyperactivity, attention problems, restlessness, and stereotyped‐repetitive behavior were reported. The aim of the study was to assess incontinence and associated psychological problems in PMD.

Methods

Forty‐one individuals with PMD were recruited through a German support group (48.8% male; mean age 13.4 years; range, 4‐55 years). Parents or caregivers completed the developmental behavior checklist (DBC), as well as the parental questionnaire: enuresis/urinary incontinence, including six questions on adaptive toileting skills.

Results

Rates of nocturnal enuresis (NE), daytime urinary incontinence, and fecal incontinence were 86%, 73%, and 79%. Rates were similar in all age groups (children, teens, adults). Constipation was present in 19%. Forty‐two percent of the sample had a clinically relevant DBC score, with adults more affected than teens. Persons with NE had significantly higher “anxiety/depression” subscale scores. Toileting skills were more developed in adults than in children. Sixty‐eight percent had further physical disabilities.

Conclusions

Incontinence rates in PMD are high in all age groups. However, persons with PMD can improve their toilet skills. Therefore, the assessment and treatment of incontinence in persons with PMD is recommended. Constipation does not seem to be a major problem in PMD. Due to the high prevalence rates of somatic conditions, an assessment for organic and functional incontinence is recommended.
On reducing the number of decision variables for dynamic optimization
Authors: Rodrigues Diogo , Bonvin Dominique
Published: October 2019

This paper presents an input parameterization for dynamic optimization that allows reducing the number of decision variables compared to traditional direct methods. A small number of decision variables is likely to be beneficial for various applications such as global optimization and real‐time optimization in the presence of plant‐model mismatch. The procedure consists of three steps: (i) adjoint‐free optimal control laws are computed for all arc types that may be present in the solution, and a finite set of plausible arc sequences is postulated; (ii) the sensitivity‐seeking arcs are either described by analytical control laws or approximated by cubic splines, which results in a parsimonious input parameterization that represents the optimal inputs using only a few parameters, namely, switching times and initial conditions for the sensitivity‐seeking arcs; and (iii) for each arc sequence, optimal parameter values are computed via numerical optimization, and the sequence with the best cost is optimal. The procedure is illustrated via the simulated examples of a semibatch reactor and a distillation column.
Prenatal diagnosis of congenital head, face, and neck malformations—Is complementary fetal MRI of value?
Authors: Zemet Roni , Amdur‐Zilberfarb Inna , Shapira Moran , Ziv‐Baran Tomer , Hoffmann Chen , Kassif Eran , Katorza Eldad
Published: October 2019

Objectives

The aim of this study was to evaluate the role of fetal magnetic resonance imaging (MRI) as a complement to ultrasound (US) in the prenatal diagnosis of craniofacial anomalies.

Methods

A historical cohort study including all pregnant women who were referred for fetal MRI because of antenatal diagnosis of craniofacial anomalies on screening US. Prenatal diagnostic US, MRI, and postnatal diagnosis were compared for consistencies and discrepancies.

Results

Forty‐five pregnant women with 73 suspected fetal craniofacial anomalies diagnosed by US underwent MRI. In 40 out of 73 anomalies (54.8%), US and MRI findings were in complete agreement with postnatal diagnoses. MRI correctly ruled out the diagnosis of 24 anomalies suspected on US and diagnosed four additional pathologies that were not demonstrated by US. Out of the 85 anomalies (suspected by imaging or confirmed postnatally), confident diagnosis could be made by MRI in 68 anomalies (80%), not diagnosed in 10 (11.8%), and over‐diagnosed in seven (8.2%). By US, confident diagnosis could be made in 44 anomalies (51.8%), not diagnosed in 11 (12.9%), and over‐diagnosed in 30 (35.3%).

Conclusion

MRI is valuable in the antenatal evaluation of fetal craniofacial anomalies and may be useful as an adjunct to US in the prenatal work‐up of craniofacial anomalies.
The role of metacognition and its indirect effect through cognitive attentional syndrome on fear of cancer recurrence trajectories: A longitudinal study
Authors: Ng Danielle W. L. , Foo Chi‐Chung , Ng Simon S. M. , Kwong Ava , Suen Dacita , Chan Miranda , Or Amy , Chun Oi Kwan , Fielding Brenna F. S. , Lam Wendy W. T.
Published: October 2019

Objective

This longitudinal study mapped distinct trajectories of fear of cancer recurrence (FCR) over 12 months among patients with breast (BC) or colorectal (CRC) cancer, and examined if metacognition, indirectly via attentional bias, intrusive thoughts and avoidance (hallmarks of cognitive attentional syndrome; CAS) predicted FCR trajectory membership.

Methods

Two hundred and seventy BC (n = 163) or CRC (n = 107) patients were assessed at 8‐weeks, 3‐, 6‐, and 12‐months postsurgery on a measure of FCR (FCRI‐SF). Metacognition (MCQ‐30), Intrusive and Avoidant Thoughts (CIES‐R) and attentional bias (dot‐probe tasks) were assessed at baseline. Latent growth mixture modeling identified FCR trajectories. Fully‐adjusted Multinomial Logistic Regression identified whether direct and indirect effects of metacognition through CAS determined FCR trajectory membership.

Results

Three distinct FCR trajectories were identified, namely, low‐stable (62.4%), high‐stable (29.2%), and recovery (8.3%). Negative beliefs about worry, cognitive confidence, and age predicted FCR trajectories (χ2 (6) = 38.31, P<.001). Compared with Low‐stable group, Recovery FCR patients held greater Negative beliefs about worry (OR = 1.13, P = .035) and High‐stable FCR patients reported poorer Cognitive confidence (OR = 1.12, P = .004). The effect of Negative beliefs about worry was partially mediated by avoidance (β = .06, 95% CIs 0.03‐0.12) and fully mediated by intrusive thoughts (β = .14, 95% CIs 0.08‐0.20). Attentional bias did not predict FCR trajectories.

Conclusions

While most patients experienced low level of FCR, 3 in 10 persistently worried about cancer returning over the first 12‐months postsurgery. Modifying metacognitive knowledge to interrupt maladaptive cognitive processing including intrusion and avoidance may be an effective therapeutic intervention for patients at risk of persistent FCR.
A systematic review of the unmet supportive care needs of men on active surveillance for prostate cancer
Authors: McIntosh Megan , Opozda Melissa J. , Evans Holly , Finlay Amy , Galvão Daniel A. , Chambers Suzanne K. , Short Camille E.
Published: October 2019

Objective

Understanding the unmet supportive care needs of men on active surveillance for prostate cancer may enable researchers and health professionals to better support men and prevent discontinuation when there is no evidence of disease progression. This review aimed to identify the specific unmet supportive care needs of men on active surveillance.

Methods

A systematic review following PRISMA guidelines was conducted. Databases (Pubmed, Embase, PsycINFO, and CINAHL) were searched to identify qualitative and/or quantitative studies that reported unmet needs specific to men on active surveillance. Quality appraisals were conducted before results were narratively synthesised.

Results

Of the 3613 unique records identified, only eight articles were eligible (five qualitative and three cross‐sectional studies). Unmet Informational, Emotional/Psychological, Social, and “Other” needs were identified. Only three studies had a primary aim of investigating unmet supportive care needs. Small active surveillance samples, use of nonvalidated measures, and minimal reporting of author reflexivity in qualitative studies were the main quality issues identified.

Conclusions

The unmet needs of men on active surveillance is an underresearched area. Preliminary evidence suggests the information available and provided to men during active surveillance is perceived as inadequate and inconsistent. Men may also be experiencing unmet psychological/emotional, social, and other needs; however, further representative, high‐quality research is required to understand the magnitude of this issue. Reporting results specific to treatment type and utilising relevant theories/models (such as the social ecological model [SEM]) is recommended to ensure factors that may facilitate unmet needs are appropriately considered and reported.
Clinical and pathologic characteristics of familial prostate cancer in Asian population
Authors: Kim Myong , Kim Jung Kwon , Ye Changhee , Lee Hakmin , Oh Jong Jin , Lee Sangchul , Jeong Seong Jin , Lee Sang Eun , Hong Sung Kyu , Byun Seok‐Soo
Published: October 2019

Background

We investigated prevalence of familial and hereditary prostate cancer (PCa) in Asian population, and compared clinical characteristics between familial and sporadic disease.

Methods

Pedigrees of 1102 patients who were treated for PCa were prospectively acquired. Clinical and pathologic characteristics and biochemical recurrence (BCR)‐free survival were compared between familial PCa and sporadic PCa in patients who underwent radical prostatectomy (RP; n = 751).

Results

The prevalence of familial, first‐degree familial, and hereditary PCa was found to be 8.4%, 6.7%, and 0.9%, respectively; similar result was obtained in patients who underwent RP (8.4%, 6.4%, and 0.9%). Patients with familial PCa were significantly younger than those with sporadic PCa (63.3 vs 65.6 years; P = .015). However, preoperative variables (prostate‐specific antigen, clinical stage, biopsy Gleason score [GS], and percentage of positive biopsy cores) and postoperative variables (surgical GS, upgrading rate, pathologic stage, and percentage of tumor volume) did not correlate with family history (P range: .114–.982). Kaplan‐Meier analysis of 5‐year BCR‐free survival revealed no significant difference between sporadic (82.7%), familial (89.4%; P = .594), and first‐degree familial (87.1%; P = .774) PCa. Analysis of p53, Bcl‐2, Ki67, and other immunohistochemistry biomarkers revealed that only increasing p53 expression and first‐degree familial PCa approached significance (P = .059).

Conclusion

The prevalence of familial PCa was somewhat lower in the Asian population than in other ethnic groups. Clinical and pathologic variables and selected histologic biomarker abnormalities were not significantly different in patients with and without a family history of PCa. BCR‐free survival following RP was also unaffected by family history.
Determination of Sapphire Off‐Cut and Its Influence on the Morphology and Local Defect Distribution in Epitaxially Laterally Overgrown AlN for Optically Pumped UVC Lasers
Authors: Enslin Johannes , Knauer Arne , Mogilatenko Anna , Mehnke Frank , Martens Martin , Kuhn Christian , Wernicke Tim , Weyers Markus , Kneissl Michael
Published: October 2019

Herein, a systematic study of the morphology and local defect distribution in epitaxially laterally overgrown (ELO) AlN on c‐plane sapphire substrates with different off‐cut angles ranging from 0.08° to 0.23° is presented. Precise measurements of the off‐cut angle α, using a combination of optical alignment and X‐ray diffraction with an accuracy of ±5° for the off‐cut direction and ±0.015° for the off‐cut angle, are carried out. For ELO AlN growth, a transition from step flow growth at α < 0.14° with height undulations on the surface to step bunching with step heights up to 20 nm for α > 0.14° is observed. Furthermore, the terraces of the step‐bunched surface exhibit curved steps. An analysis of the local defect distribution by scanning transmission electron microscopy and a comparison with atomic force microscopy reveal a bunching of defects in line with the ELO pattern and a roughening of step edges in highly defective regions. In addition, a reduction in the threshold excitation power density for optically pumped ultraviolet‐C (UVC) lasers with smooth surface morphologies is observed.
Hydrogen Gas Adsorption on Pd‐ and Pt‐Decorated GaN (0001) Surface: A First‐Principles Study
Authors: Wang Hengshan , Zhang Heqiu , Liu Jun , Xue Dongyang , Liang Hongwei , Xia Xiaochuan
Published: October 2019

Herein, density functional theory (DFT) calculations are carried out to investigate the hydrogen gas adsorption on the Pd(Pt)‐decorated GaN (0001) surface. It is found that the diffusion barrier of Pd (Pt) on the GaN (0001) surface is 0.3996 (0.602) eV. Hydrogen molecule adsorbed on the Pt‐decorated GaN (0001) surface can dissociate into hydrogen atoms. The comparison of the density of states and Mulliken charge analysis of the hydrogen molecule adsorption on the Pd(Pt)‐decorated GaN (0001) surface are analyzed in detail. The Pt‐decorated GaN (0001) surface is found to have a high sensing ability for hydrogen molecules from the theoretical point of view.
Quantification of dopant species using atom probe tomography for semiconductor application
Authors: Yeoh Wai Kong , Hung Shih‐Wei , Chen Shih‐Che , Lin Yi‐Hsiang , Lee Jang Jung
Published: October 2019

Doping of semiconductors serve various purposes in metal‐oxide‐semiconductor (CMOS) technology, eg, increase carrier concentration and modify electric field distribution. With the scaling down of device and the introduction of three‐dimensional fin field‐effect transistors (FinFET), precise and reliable dopant quantification of concentration at the nano‐scale is critical. Laser‐assisted atom probe tomography (APT) provides a unique approach to characterize and quantify the dopant in three dimensions at sub‐nanometer resolution. Nevertheless, quantification accuracy of APT is strongly influenced by the experimental conditions. Although B quantification has been widely studied, the correlation of B signal loss to B concentration is not yet established. In addition, no phosphorous quantification study has been reported. In this work, we found that, due to B multi‐hit effect in APT, high B dose sample has larger B loading compared with low B dose sample. For standard calibration with minimized impact from multi‐hit effect, we recommend B dose in the range of 1e14 atoms/cm2. Despite the fact that B loading is dose dependent, APT quantification of B achieves precision within 2% to 6% relative standard deviation (RSD), which demonstrates that APT has good accuracy. On the other hand, P quantification suffers from mass interference of 31P+ and 31P22+ at 31 Da resulting in a large loading between APT and secondary ion mass spectrometry (SIMS). Nevertheless, we recommend that 31 Da to be labeled as 31P+ for smaller P variation for the APT analysis.
Capillary‐Based Microfluidics—Coflow, Flow‐Focusing, Electro‐Coflow, Drops, Jets, and Instabilities
Authors: Guerrero Josefa , Chang Ya‐Wen , Fragkopoulos Alexandros A. , Fernandez‐Nieves Alberto
Published: October 2019

Capillary‐based microfluidics is a great technique to produce monodisperse and complex emulsions and particulate suspensions. In this review, the current understanding of drop and jet formation in capillary‐based microfluidic devices for two primary flow configurations, coflow and flow‐focusing is summarized. The experimental and theoretical description of fluid instabilities is discussed and conditions for controlled drop breakup in different modes of drop generation are provided. Current challenges in drop breakup with low interfacial tension systems and recent progress in overcoming drop size limitations using electro‐coflow are addressed. In each scenario, the physical mechanisms for drop breakup are revisited, and simple scaling arguments proposed in the literature are introduced.
Multiconfiguration Dirac–Fock calculations of Zn K‐shell radiative and nonradiative transitions
Authors: Martins Luís , Amaro Pedro , Pessanha Sofia , Guerra Mauro , Machado Jorge , Carvalho Maria Luisa , Santos José Paulo
Published: October 2019

Zinc K‐shell radiative and radiationless transition rates are calculated using the multiconfiguration Dirac–Fock method. Correlation up to the 4p orbital is included in almost all transition rate calculations. Calculated radiative transition rates and transition probabilities are compared with Scofield's Dirac–Hartree–Slater and Dirac–Hartree–Fock calculations, presenting good agreement with the later. Radiative transition intensity ratios involving the strongest lines are compared with theoretical, experimental, and empirical‐fit values. Most ratios are in close agreement with the empirical‐fit values from NIST's Fundamental Parameters database. Calculated radiationless transition rates and ratios are compared with Chen et al.'s Dirac–Fock values and Safronova et al.'s Dirac–Fock values. The K‐LL transition rates are overall lower than Chen et al.'s values, whereas the K‐LX and K‐XY transition rates are overall higher. Calculated K‐LX/K‐LL and K‐XY/K‐LL ratios are relatively close to the experimental values compared. Some calculated intensities relative to K‐L
are in good agreement with the experimental values, whereas others present worse agreement. The calculated fluorescence yield is higher than all theoretical, experimental, and empirical‐fitted values compared, probably because the total radiationless transition rate value calculated in the present work is relatively low.
Relativistic effect of J/𝜓 hadroproduction in large pT region
Authors: Li Rong , Chen An-Ping , Huang Jing-Kai , Ma Yan-Qing
Published: October 2019

Abstract

By combining NRQCD factorization and collinear factorization, we compute a series of relativistic corrections for J/𝜓 hadroproduction to all orders in 𝜐2 at large p

T
limit. The 𝜐2 expansion converges well for all channels. We find that the ratio of relativistic correction term to the corresponding leading term is independent of kinematic variables for any channel, which generalizes the proportional relations found in previous works to all orders.
Spin-2 excitations in Gaiotto-Maldacena solutions
Authors: Itsios Georgios , Penín José Manuel , Zacarías Salomón
Published: October 2019

Abstract

In this paper we study spin-2 excitations for a class of N = 2 supersymmetric solutions of type-IIA supergravity found by Gaiotto and Maldacena. The mass spectrum of these excitations can be derived by solving a second order partial differential equation. As specific examples of this class we consider the Abelian and non-Abelian T-dual versions of the AdS5 × S
5 and we study the corresponding mass spectra. For the modes that do not “feel” the (non-)Abelian T-duality transformation we provide analytic formulas for the masses, while for the rest we were only able to derive the spectra numerically. The numerical values that correspond to large masses are compared with WKB approximate formulas. We also find a lower bound for the masses. Finally, we study the field theoretical implications of our results and propose dual spin-2 operators.
Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells
Authors: Meneses-Salas Elsa , García-Melero Ana , Kanerva Kristiina , Blanco-Muñoz Patricia , Morales-Paytuvi Frederic , Bonjoch Júlia , Casas Josefina , Egert Antonia , Beevi Syed S. , Jose Jaimy , Llorente-Cortés Vicenta , Rye Kerry-Anne , Heeren Joerg , Lu Albert , Pol Albert , Tebar Francesc , Ikonen Elina , Grewal Thomas , Enrich Carlos , Rentero Carles
Published: October 2019

Cholesterol accumulation in late endosomes is a prevailing phenotype of Niemann-Pick type C1 (NPC1) mutant cells. Likewise, annexin A6 (AnxA6) overexpression induces a phenotype reminiscent of NPC1 mutant cells. Here, we demonstrate that this cellular cholesterol imbalance is due to AnxA6 promoting Rab7 inactivation via TBC1D15, a Rab7-GAP. In NPC1 mutant cells, AnxA6 depletion and eventual Rab7 activation was associated with peripheral distribution and increased mobility of late endosomes. This was accompanied by an enhanced lipid accumulation in lipid droplets in an acyl-CoA:cholesterol acyltransferase (ACAT)-dependent manner. Moreover, in AnxA6-deficient NPC1 mutant cells, Rab7-mediated rescue of late endosome-cholesterol export required the StAR-related lipid transfer domain-3 (StARD3) protein. Electron microscopy revealed a significant increase of membrane contact sites (MCS) between late endosomes and ER in NPC1 mutant cells lacking AnxA6, suggesting late endosome-cholesterol transfer to the ER via Rab7 and StARD3-dependent MCS formation. This study identifies AnxA6 as a novel gatekeeper that controls cellular distribution of late endosome-cholesterol via regulation of a Rab7-GAP and MCS formation.
Targeting intrinsically disordered proteins involved in cancer
Authors: Santofimia-Castaño Patricia , Rizzuti Bruno , Xia Yi , Abian Olga , Peng Ling , Velázquez-Campoy Adrián , Neira José L. , Iovanna Juan
Published: October 2019

Intrinsically disordered proteins (IDPs) do not have a well-defined structure under physiological conditions, but they have key roles in cell signaling and regulation, and they are frequently related to the development of diseases, such as cancer and other malignancies. This has converted IDPs in attractive therapeutic targets; however, targeting IDPs is challenging because of their dynamic nature. In the last years, different experimental and computational approaches, as well as the combination of both, have been explored to identify molecules to target either the hot-spots or the allosteric sites of IDPs. In this review, we summarize recent developments in successful targeting of IDPs, all of which are involved in different cancer types. The strategies used to develop and design (or in one particular example, to repurpose) small molecules targeting IDPs are, in a global sense, similar to those used in well-folded proteins: (1) screening of chemically diverse or target-oriented compound libraries; or (2) study of the interfaces involved in recognition of their natural partners, and design of molecular candidates capable of binding to such binding interface. We describe the outcomes of using these approaches in targeting IDPs involved in cancer, in the view to providing insight, to target IDPs in general. In a broad sense, the designed small molecules seem to target the most hydrophobic regions of the IDPs, hampering macromolecule (DNA or protein)–IDP interactions; furthermore, in most of the molecule–IDP complexes described so far, the protein remains disordered.
Microaerobic conditions caused the overwhelming dominance of Acinetobacter spp. and the marginalization of Rhodococcus spp. in diesel fuel/crude oil mixture-amended enrichment cultures
Authors: Révész Fruzsina , Figueroa-Gonzalez Perla Abigail , Probst Alexander J. , Kriszt Balázs , Banerjee Sinchan , Szoboszlay Sándor , Maróti Gergely , Táncsics András
Published: October 2019

The aim of the present study was to reveal how different microbial communities evolve in diesel fuel/crude oil-contaminated environments under aerobic and microaerobic conditions. To investigate this question, aerobic and microaerobic bacterial enrichments amended with a diesel fuel/crude oil mixture were established and analysed. The representative aerobic enrichment community was dominated by Gammaproteobacteria (64.5%) with high an abundance of Betaproteobacteriales (36.5%), followed by Alphaproteobacteria (8.7%), Actinobacteria (5.6%), and Candidatus Saccharibacteria (4.5%). The most abundant alkane monooxygenase (alkB) genotypes in this enrichment could be linked to members of the genus Rhodococcus and to a novel Gammaproteobacterium, for which we generated a high-quality draft genome using genome-resolved metagenomics of the enrichment culture. Contrarily, in the microaerobic enrichment, Gammaproteobacteria (99%) overwhelmingly dominated the microbial community with a high abundance of the genera Acinetobacter (66.3%), Pseudomonas (11%) and Acidovorax (11%). Under microaerobic conditions, the vast majority of alkB gene sequences could be linked to Pseudomonas veronii. Consequently, results shed light on the fact that the excellent aliphatic hydrocarbon degrading Rhodococcus species favour clear aerobic conditions, while oxygen-limited conditions can facilitate the high abundance of Acinetobacter species in aliphatic hydrocarbon-contaminated subsurface environments.
Lysyl oxidases: linking structures and immunity in the tumor microenvironment
Authors: Tenti Paolo , Vannucci Luca
Published: October 2019

The lysyl oxidases (LOXs) are a family of enzymes deputed to cross-link collagen and elastin, shaping the structure and strength of the extracellular matrix (ECM). However, many novel “non-canonical” functions, alternative substrates, and regulatory mechanisms have been described and are being continuously elucidated. The activity of LOXs, therefore, appears to be integrated into a complex network of signals regulating many cell functions, including survival/proliferation/differentiation. Among these signaling pathways, TGF-β and PI3K/Akt/mTOR, in particular, cross-talk extensively with each other and with LOXs also initiating complex feedback loops which modulate the activity of LOXs and direct the remodeling of the ECM. A growing body of evidence indicates that LOXs are not only important in the homeostasis of the normal structure of the ECM, but are also implicated in the establishment and maturation of the tumor microenvironment. LOXs’ association with advanced and metastatic cancer is well established; however, there is enough evidence to support a significant role of LOXs in the transformation of normal epithelial cells, in the accelerated tumor development and the induction of invasion of the premalignant epithelium. A better understanding of LOXs and their interactions with the different elements of the tumor immune microenvironment will prove invaluable in the design of novel anti-tumor strategies.
Disease Severity and Cost in Adhesive Small Bowel Obstruction
Authors: Hernandez Matthew C. , Finnesgard Eric J. , Shariq Omair A. , Knight Ariel , Stephens Daniel , Aho Johnathon M. , Kim Brian D. , Schiller Henry J. , Zielinski Martin D.
Published: October 2019

Background

Adhesive small bowel obstruction (ASBO) severity has been associated with important clinical outcomes. However, the impact of ASBO severity on hospitalization cost is unknown. The American Association for the Surgery of Trauma (AAST) developed an Emergency General Surgery (EGS) disease severity grading system for ASBO. We stratified patients’ ASBO severity and captured hospitalization costs hypothesizing that increased disease severity would correlate with greater costs.

Methods

This was a single‐center study of hospitalized adult patients with SBO during 2015–2017. Clinical data and estimated total cost (direct + indirect) were abstracted. AAST EGS grades (I–IV) stratified disease severity. Costs were normalized to the median grade I cost. Univariate and multivariate analyses evaluated the relationship between normalized cost and AAST EGS grade, length of hospital and ICU stay, operative time, and Charlson comorbidity index.

Results

There were 214 patients; 119 (56%) were female. AAST EGS grades included: I (62%, n = 132), II (23%, n = 49), III (7%, n = 16), and IV (8%, n = 17). Relative to grade I, median normalized cost increased by 1.4‐fold for grade II, 1.6‐fold for grade III, and 4.3‐fold for grade IV disease. No considerable differences in patient comorbidity between grades were observed. Pair‐wise comparisons demonstrated that grade I disease cost less than higher grades (corrected p < 0.001). Non‐operative management was associated with lower normalized cost compared to operative management (1.1 vs. 4.5, p < 0.0001). In patients who failed non‐operative management, normalized cost was increased 7.2‐fold. Collectively, the AAST EGS grade correlated well with cost (Spearman's p = 0.7, p < 0.0001). After adjustment for covariates, AAST EGS grade maintained a persistent relationship with cost.

Conclusion

Increasing ASBO severity is independently associated with greater costs. Efforts to identify and mitigate costs associated with this burdensome disease are warranted.

Level of evidence

III, economic/decision.
Altered serum level of metabolic and endothelial factors in patients with systemic sclerosis
Authors: Stochmal Anna , Czuwara Joanna , Zaremba Michał , Rudnicka Lidia
Published: October 2019

Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by progressive fibrosis, vascular impairment and immune abnormalities. In recent years, adipokines (mediators synthetized by adipose tissue) have been indicated as a possible missing link in the pathogenesis of SSc. The aim of this study was to investigate the serum concentration of metabolic adipose tissue factors: adiponectin, resistin, leptin and endothelial proteins: endothelin-1, fractalkine and galectin-3 in patients with systemic sclerosis. The study included 100 patients with confirmed SSc diagnosis and 20 healthy individuals. The concentration of respective proteins was determined by enzyme-linked immunosorbent assay. The following markers showed statistically significant increased mean concentrations in patients with SSc in comparison to healthy control: resistin (13.41 vs 8.54 ng/mL; P = 0.0012), endothelin-1 (1.99 vs 1.31 pg/mL; P = 0.0072) and fractalkine (2.93 vs 1.68 ng/mL; P = 0.0007). Elevated serum levels of galectin-3 (4.54 vs 3.26 ng/mL; P = 0.0672) and leptin (19,542 vs 14,210 pg/mL; P = 0.1817) were observed. Decreased concentration of adiponectin was found in patients with SSc (5150 vs 8847 pg/mL; P = 0.0001). Fractalkine and galectin-3 levels were significantly higher in diffuse cutaneous SSc than limited cutaneous SSc subset (3.93 ng/mL vs 2.58 ng/mL, P = 0.0018; 6.86 ng/mL vs 3.78 ng/mL, P = 0.0008, respectively) and correlated positively with modified Rodnan Skin Score in total SSc patients (r = 0.376, P = 0.0009; r = 0.236, P = 0.018, respectively). In conclusion, an increased serum level of resistin associated with increased endothelin-1 and fractalkine level and decreased adiponectin level may indicate a significant role of the adipose tissue in the development and progression of vascular abnormalities in patients with systemic sclerosis. Fractalkine and galectin-3 may participate in promoting and exacerbating the fibrotic process in SSc.
Evaluation of disk halo size after small incision lenticule extraction (SMILE)
Authors: Han Tian , Zhao Feng , Chen Xun , Miao Huamao , Chen Zhuoyi , Zhou Xingtao
Published: October 2019

Purpose

To investigate changes in objective disk halo size produced by a glare source after small incision lenticule extraction (SMILE) for myopia correction.

Methods

This prospective clinical study included 45 right eyes of 45 patients with a mean age of 25.40 ± 5.06 years and mean spherical equivalent (SE) of − 6.08 ± 1.90 diopters. Disk halo size was measured with a vision monitor before surgery and at postoperative 1 week and 3 months. Other information was collected, including age, SE, lenticule thickness, lenticule diameter, dark pupil, and pupillary response to light parameters (initial diameter; amplitude, latency, duration, and velocity of contraction; latency, duration, and velocity of dilation; and maximum, minimum, and average pupil size).

Results

Compared to preoperative values, disk halo size increased significantly at postoperative 1 week (P = 0.026) and returned to baseline at postoperative 3 months (P = 0.349). Preoperative disk halo size significantly correlated with SE (r = − 0.346, P = 0.020), minimum pupil size (r = 0.365, P = 0.014), and average pupil size (r = 0.310, P = 0.038). Disk halo size at postoperative 1 week was significantly correlated with age (r = 0.324, P = 0.030) and minimum pupil size (r = 0.297, P = 0.047). Disk halo size at postoperative 3 months was significantly correlated with lenticule diameter (r = − 0.362, P = 0.015), initial diameter (r = 0.311, P = 0.037), maximum pupil size (r = 0.312, P = 0.037), minimum pupil size (r = 0.440, P = 0.002), and average pupil size (r = 0.373, P = 0.012).

Conclusions

After SMILE, disk halo size demonstrated a temporary increase and then returned to baseline.
Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication
Authors: Take Susumu , Mizuno Motowo , Ishiki Kuniharu , Kusumoto Chiaki , Imada Takayuki , Hamada Fumihiro , Yoshida Tomowo , Yokota Kenji , Mitsuhashi Toshiharu , Okada Hiroyuki
Published: October 2019

Background and aims

Eradication of Helicobacter pylori reduces the risk of gastric cancer. In this study, we investigated the risk beyond 10 years after eradication of H. pylori.

Methods

We conducted a retrospective cohort study of 2737 patients who had yearly endoscopic follow-up after cure of H. pylori infection. For comparison of gastric cancer risk in the second decade of follow-up with that in the first decade, we calculated standardized incidence ratios (SIRs) by dividing the number of observed cases of gastric cancer in the second decade of follow-up by that of expected cases which was estimated using the incidence rate ratio of age in the first decade.

Results

During the follow-up for as long as 21.4 years (mean 7.1 years), gastric cancer developed in 68 patients (0.35% per year). The SIRs for diffuse-type gastric cancer was infinity (0 expected case and 4 observed cases) in patients with mild gastric mucosal atrophy and 10.9 (95% confidence interval 4.53–26.1) with moderate atrophy, whereas no significant increase of SIRs was observed in intestinal-type cancer regardless of the grade of baseline gastric atrophy or in diffuse-type cancer in patients with severe atrophy even though who had the highest risk.

Conclusions

The longer the follow-up, the greater the risk of developing diffuse-type gastric cancer becomes in patients with mild-to-moderate gastric atrophy at baseline. Endoscopic surveillance should be continued beyond 10 years after cure of H. pylori irrespective of the severity of gastric atrophy.
Long-term clinical outcome of two revision strategies for failed total disc replacements
Authors: Kitzen J. , Vercoulen T. F. G. , van Kuijk S. M. J. , Schotanus M. G. M. , Kort N. P. , van Rhijn L. W. , Willems P. C. P. H.
Published: October 2019

Purpose

To compare the long-term clinical results and complications of two revision strategies for patients with failed total disc replacements (TDRs).

Methods

In 19 patients, the TDR was removed and the intervertebral defect was filled with a femoral head bone strut graft. In addition, instrumented posterolateral fusion was performed (removal group). In 36 patients, only a posterolateral instrumented fusion was performed (fusion group). Visual Analogue Scale (VAS) for pain and Oswestry Disability Index (ODI) were completed pre- and post-revision surgery. Intra- and post-operative complications of both revision strategies were assessed.

Results

The median follow-up was 12.3 years (range 5.3–24.3). In both the removal and fusion groups, a similar (p = 0.515 and p = 0419, respectively) but significant decrease in VAS (p = 0.001 and p = 0.001, respectively) and ODI score (p = 0.033 and p = 0.013, respectively) at post-revision surgery compared to pre-revision surgery was seen. A clinically relevant improvement in VAS and ODI score was found in 62.5% and 43.8% in the removal group and in 43.5% and 39.1% in the fusion group (p = 0.242 and p = 0.773, respectively). Removal of the TDR was associated with substantial intra-operative complications such as major vessel bleeding and ureter lesion. The percentage of late re-operations for complications such as pseudarthrosis were comparable for both revision strategies.

Conclusions

Revision of a failed TDR is clinically beneficial in about half of the patients. No clear benefits for additional TDR removal as compared to posterolateral instrumented fusion alone could be identified. In particular, when considering the substantial risks and complications, great caution is warranted with removal of the TDR.

Graphic abstract

These slides can be retrieved under Electronic Supplementary Material.
Total extraperitoneal endoscopic hernioplasty (TEP) versus Lichtenstein hernioplasty: a systematic review by updated traditional and cumulative meta-analysis of randomised-controlled trials
Authors: Gavriilidis P. , Davies R. J. , Wheeler J. , de’Angelis N. , Di Saverio S.
Published: October 2019

Background–purpose

Totally extraperitoneal (TEP) endoscopic hernioplasty and Lichtenstein hernioplasty are the most commonly used approaches for inguinal hernia repair. However, current evidence on which is the preferred approach is inconclusive. This updated meta-analysis was conducted to track the accumulation of evidence over time.

Methods

Studies were identified by a systematic literature search of the EMBASE, PubMed, Cochrane Library, and Google Scholar databases. Fixed- and random-effects models were used to cumulatively assess the accumulation of evidence over time.

Results

The TEP cohort showed significantly higher rates of recurrences and vascular injuries compared to the Lichtenstein cohort; [Peto Odds ratio (OR) = 1.58 (1.22, 2.04), p = 0.005], [Peto OR = 2.49 (1.05, 5.88), p = 0.04], respectively. In contrast, haematoma formation rate, time to return to usual activities, and local paraesthesia were significantly lower in the TEP cohort compared to the Lichtenstein cohort; [Peto OR = 0.26 (0.16, 0.41), p ≤ 0.001], [mean difference = − 6.32 (− 8.17, − 4.48), p ≤ 0.001], [Peto OR = 0.26 (0.17, 0.40), p ≤ 0.001], respectively.

Conclusions

This study, which is based on randomised-controlled trials (RCTs) of high quality, showed significantly higher rates of recurrences and vascular injuries in the TEP cohort than in the Lichtenstein cohort. In contrast, rate of postoperative haematoma formation, local paraesthesia, and time to return to usual activities were significantly lower in the TEP cohort than in the Lichtenstein cohort. Future multicentre RCTs with strict adherence to the standards recommended in the Consolidated Standards of Reporting Trials guidelines will shed further light on the topic.
Obesity paradox in subarachnoid hemorrhage: a systematic review
Authors: Rautalin Ilari , Kaprio Jaakko , Korja Miikka
Published: October 2019

As the number of obese people is globally increasing, reports about the putative protective effect of obesity in life-threatening diseases, such as subarachnoid hemorrhage (SAH), are gaining more interest. This theory—the obesity paradox—is challenging to study, and the impact of obesity has remained unclear in survival of several critical illnesses, including SAH. Thus, we performed a systematic review to clarify the relation of obesity and SAH mortality. Our study protocol included systematic literature search in PubMed, Scopus, and Cochrane library databases, whereas risk-of-bias estimation and quality of each selected study were evaluated by the Critical Appraisal Skills Program and Cochrane Collaboration guidelines. A directional power analysis was performed to estimate sufficient sample size for significant results. From 176 reviewed studies, six fulfilled our eligibility criteria for qualitative analysis. One study found paradoxical effect (odds ratio, OR = 0.83 (0.74–0.92)) between morbid obesity (body mass index (BMI) > 40) and in-hospital SAH mortality, and another study found the effect between continuously increasing BMI and both short-term (OR = 0.90 (0.82–0.99)) and long-term SAH mortalities (OR = 0.92 (0.85–0.98)). However, according to our quality assessment, methodological shortcomings expose all reviewed studies to a high-risk-of-bias. Even though two studies suggest that obesity may protect SAH patients from death in the acute phase, all reviewed studies suffered from methodological shortcomings that have been typical in the research field of obesity paradox. Therefore, no definite conclusions could be drawn.
Longer small bowel segments are resected in emergency surgery for ileocaecal Crohn’s disease with a higher ileostomy and complication rate
Authors: Celentano V. , O’Leary D. P. , Caiazzo A. , Flashman K. G. , Sagias F. , Conti J. , Senapati A. , Khan J.
Published: October 2019

Background

Repeated intestinal resections may have disabling consequences in patients with Crohn’s disease even in the absence of short bowel syndrome. Our aim was to evaluate the length of resected small bowel in patients undergoing elective and emergency surgery for ileocolic Crohn’s disease.

Methods

A prospective observational study was conducted on patients undergoing surgery for ileocolonic Crohn’s disease in a single colorectal centre from May 2010 to April 2018. The following patients were included: (1) patients with first presentation of ileocaecal Crohn’s disease undergoing elective surgery; (2) patients with ileocaecal Crohn’s disease undergoing emergency surgery; (3) patients with recurrent Crohn’s disease of the distal ileum undergoing elective surgery. The primary outcomes were length of resected small bowel and the ileostomy rate. Operating time, complications and readmissions within 30 days were the secondary outcomes.

Results

One hundred and sixty-eight patients were included: 87 patients in the elective primary surgery group, 50 patients in the emergency surgery group and 31 in the elective redo surgery group. Eleven patients (22%) in the emergency surgery group had an ileostomy compared to 10 (11.5%) in the elective surgery group (p < 0.0001). In the emergency surgery group the median length of the resected small bowel was 10 cm longer than into the group having elective surgery for primary Crohn’s disease.

Conclusions

Patients undergoing emergency surgery for Crohn’s disease have a higher rate of stoma formation and 30-day complications. Laparoscopic surgery in the emergency setting has a higher conversion rate and involves resection of longer segments of small bowel.