bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

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

AbstractCapillary‐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.
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

AbstractCholesterol 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

Abstract
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

Abstract
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

AbstractThe 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

AbstractBackgroundAdhesive 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.MethodsThis 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.ResultsThere 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.ConclusionIncreasing ASBO severity is independently associated with greater costs. Efforts to identify and mitigate costs associated with this burdensome disease are warranted.Level of evidenceIII, 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

Abstract
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

AbstractAs 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.