Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and safety of bevacizumab-based maintenance therapy in metastatic colorectal cancer

Abstract Objective: To identify the optimal treatment strategy after first-line induction chemotherapy for metastatic colorectal cancer (mCRC). Methods: We conducted a meta-analysis of randomized controlled trials comparing bevacizumab-based maintenance therapy, observation, and continuous chemotherapy. We searched the PubMed, Embase, and Cochrane databases for relevant articles published through March 2018. All randomized phase-III trials evaluating bevacizumab-based maintenance treatment after bevacizumab-based induction treatment were eligible for inclusion. The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. Hazard ratios (HRs) with 95% confidence intervals (CIs) or data for calculating HRs with 95% CIs were extracted. The RevMan v5.3 (Copenhagen, Denmark) software was used for data analysis. Results: Nine trials (3121 patients) were included in this meta-analysis. Compared with observation alone, bevacizumab-based maintenance therapy significantly improved PFS (HR: 0.62, 95% CI: 0.47–0.82) and showed a trend toward prolonged OS (HR: 0.93, 95% CI: 0.83–1.05). The incidence of grade 3/4 toxicity, including hypertension and fatigue, was higher after maintenance therapy than after observation alone. PFS (HR: 0.91, 95% CI: 0.70–1.18) and OS (HR: 0.88, 95% CI: 0.74–1.04) did not differ between the maintenance treatment and continuous chemotherapy groups. Grade 3/4 toxicity, including diarrhea and sensory neuropathy, was less common after maintenance therapy than after continuous chemotherapy. Conclusion: Bevacizumab-based maintenance therapy significantly improved PFS, showed a trend toward prolonged OS, and reduced cumulative grade 3/4 toxicity relative to continuous chemotherapy with comparable efficacy. Although maintenance therapy was beneficial, the optimal strategy should be individualized.
Cardiopulmonary function after robotic exoskeleton-assisted over-ground walking training of a patient with an incomplete spinal cord injury

Abstract Rationale: Spinal cord injury (SCI) patients who experience difficulties with independent walking use gait-assistive devices such as a cane, walker, or wheelchair. Few studies have explored gait patterns or cardiopulmonary function in chronic SCI patients after powered exoskeleton training. We investigated whether the cardiopulmonary function of a patient with an incomplete chronic cervical SCI and a hemiplegic gait pattern could be improved by walking training using a powered exoskeleton (Angelegs). Patient concerns: A 57-year-old male was diagnosed with an SCI at C3-C4. The right upper and lower limb motor functions differed when evaluated before entry into the program. Motor function was good in the right leg but poor in the left one. Before program entry, the patient could walk for about 10 m using a cane. He did not have a history of severe medical or psychological problems and was not cognitively impaired. Diagnosis: The patient was tetraplegia with incomplete SCI at C3-C4. Interventions: The patient was trained for 6 weeks using a powered exoskeleton. The training program consisted of sit-to-stand and stand-to-sit movements, maintenance of balanced standing for 5 minutes, and walking for 15 minutes. Outcomes: After 6 weeks of training, gait speed improved in the timed up-and-go test, and cardiac function was enhanced as measured by the metabolic equivalent and VO2 tests. Lessions: Walking training using a powered exoskeleton can facilitate the effective rehabilitation and improve the gait speed and cardiopulmonary function of patients with chronic SCIs or strokes.
Restoration of the inferomedial orbital strut using a standardized three‐dimensional printing implant

The inferomedial orbital strut (IOS) is the thin bony junction of the orbital medial wall and floor. Its fracture is common and leads to serious complications, including enophthalmos, globe dystopia and diplopia. However, anatomical restoration of the IOS is challenging owing to reduced structural support; sound anatomical background and accurate implants are therefore essential. The aim of the present study was to incorporate data from cadaveric orbit anatomy into three‐dimensional (3D) printing technology and to reconstruct the complex orbital fracture elaborately. After averaging the data from computed tomography (CT) images of 100 adult cadavers, the dimensions of the IOS were extracted, and a tangent sphere was created using a computer‐aided design program. The curves were compared with the CT data of 10 adult patients from the simulation test. Based on these data, a standardized 3D implant, 1.15 mm thick, was designed using polycaprolactone. The implant was placed in five patients with complex orbital fractures. The radius of the sphere in contact with the orbit, measuring 33.54 mm, was confirmed to be appropriate. A comparison between the normal side volume (V0) and the postoperative volume (Vpost) showed that they were statistically similar. Furthermore, a comparison between V0 and the preoperative volume (Vpre), and Vpost compared with Vpre also showed a statistically significant difference (P < 0.05). On follow‐up, the preoperative ocular symptoms were resolved. The orbital data obtained from 100 cadavers provided standardized orbital anatomy, and 3D printed implants were created. The implants were anatomically accurate with regard to the orbital cavity and adequately covered the simulation model. The implant also showed satisfactory results when applied clinically in actual patients.
Membrane fusion and infection abilities of baculovirus virions are preserved during freezing and thawing in the presence of trehalose

ABSTRACT Budded viruses (BVs) of baculovirus such as Autographa californica nucleopolyhedrovirus (AcNPV) have recently been studied as biological nanomaterials, and methods for their longer-term storage without deterioration would be desirable. The cryopreservation of virions with a naturally occurring saccharide like trehalose as a cryoprotectant is known to be useful for maintaining the viral structure and function. In this study, we examined how useful trehalose is as protectant for BV cryopreservation during repeated freeze-thaw cycles: 1) membrane fusion between liposomes (multilamellar vesicles, MLVs) and BVs, 2) infection of insect culture cells (Sf9 cells) by RFP-expressing BVs, and 3) morphologies of these BVs were investigated by fluorescent dequenching assay, fluorescence microscopy, and transmission electron microscopy (TEM), respectively. The results suggest that the BVs deteriorate in quality with each freeze-thaw cycle, and this deterioration can be diminished with the use of trehalose to an extent similar to that seen with storage on ice. GRAPHICAL ABSTRACT Trehalose serves as a cryoprotectant on baculovirus budded virus particles during repeated freeze-thaw cycles.
CSF angiogenin levels in amyotrophic lateral Sclerosis-Frontotemporal dementia spectrum

Abstract Objective: Angiogenin (ANG) is a pro-angiogenic and neurotrophic factor with an important role in stress-induced injury, by promoting neovascularization and neuronal survival. Identification of loss-of-function mutations and evidence of beneficial effect of ANG administration in transgenic SOD1G93A mice have linked ANG to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), stimulating interest in considering circulating ANG levels as an ALS disease biomarker although robust evidence is still lacking. Aim of our study was to assess differences of ANG levels in the cerebrospinal fluid (CSF) of a large cohort of patients with ALS and frontotemporal dementia (FTD) compared to controls and to explore correlations between ANG content and disease-related clinical variables. Methods: ANG levels were measured in CSF samples using a commercially available ELISA kit in 88 patients affected with ALS and/or FTD and 46 unrelated individuals (control group). Results: ANG levels didn’t differ significantly between cases and controls. Patients with FTD or ALS-FTD showed significantly increased CSF concentration of ANG compared to ALS patients without dementia and controls in a multivariate regression model (p < 0.001). No correlations were found in ALS/FTD patients between ANG levels and clinical parameters, including age, presence of C9orf72 repeat expansion, body mass index (BMI). Conclusions: our findings highlight a role of ANG as CSF biomarker useful to identify ALS patients with concurrent FTD and suggest that it should be further explored as potential biomarker for FTD.
Late hyaluronidase injection in local anesthesia: Morphofunctional evaluation in rat sciatic nerve block

Introduction: Despite the enhancing effects of hyaluronidase (HYAL) over duration of anesthesia, this enzyme could cause adverse effects when injected concomitantly with local anesthetics in dental blocks. Objective: This study aimed to assess the tissue alterations caused by a local anesthetic protocol consisting of a late HYAL injection and confirm its functional effectiveness. Materials and Methods: The protocol efficacy was proved by evaluating sensory and motor functions in rats. The sciatic nerve was blocked with 2% lidocaine (LID) with epinephrine (n = 25). Thirty minutes later, 75 TRU/ml HYAL was injected into the same site (experimental group, LID/HYAL). One week later, this protocol was repeated in the contralateral hindlimb, injecting only HYAL's vehicle (control group, LID/vehicle [LID/V]). To observe the integrity of the local tissues, histological specimens were obtained 1, 24, 48, and 72 h after treatment with LID/HYAL or LID/V (n = 16 each) and stained with hematoxylin/eosin and picrosirius red. Results: Local inflammation was similar in both groups. The integrity of the nerve fibers was preserved, in spite of some inflammation-associated injuries in the surrounding tissues. The reversible tissue disorganization caused by HYAL, probably facilitated the diffusion of the residual anesthetic to the nerve, resulting in a prolonged anesthetic effect (P < 0.05). Conclusions: No irreversible morphological alterations are caused by the administration of HYAL prior the end of the LID-induced block. Moreover, this protocol prolongs LID's anesthetic effect.
Cross-sectional associations between the diversity of sport activities and the type of low back pain in adulthood

Abstract Leisure-time physical activity has a complex relationship with low back pain (LBP). Thus, we aimed to investigate whether the diversity of sport activities is associated with the type of LBP. In the FinnTwin16 study, 4246 (55% females) Finnish twins at mean age 34.1 years replied to a health behaviour survey in 2010–2012. Based on the participation in different sport activities, we created two measures of diversity: quantity (i.e. the number of sport activities: 1, 2, 3, 4 and ≥5) and quality (i.e. the type of sport activity: endurance, strength, body care, etc.). Based on the frequency, duration and type of LBP, we created three groups: no history of LBP lasting more than one day, radiating LBP and non-radiating LBP. The associations between the quantity and quality of sport activities and the type of LBP were investigated with logistic regression analyses. Participation in ≥5 sport activities associated with less radiating and non-radiating LBP in analyses pooled across sex (odds ratio 0.46, 95% CI 0.30–0.69 and 0.66, 0.44–0.99, respectively). However, the associations attenuated after adjusting for several confounders. Participation in endurance sports was associated with less radiating (0.58, 0.43–0.76) and non-radiating (0.60, 0.44–0.81) LBP, whereas strength sports and body care only with less radiating LBP (0.76, 0.58–1.00 and 0.26, 0.09–0.74, respectively) adjusted for all sport types. On a sport-specific level, running and cycling were associated with less radiating and non-radiating LBP. In adulthood, the diversity of sport activities, particularly participation in endurance sports, may be associated with less radiating and non-radiating LBP.
Light-driven carbon−carbon bond formation via CO2 reduction catalyzed by complexes of CdS nanorods and a 2-oxoacid oxidoreductase

Significance Nature uses enzymes to catalyze a vast array of complex chemical reactions. Enzymes that catalyze reduction reactions require partners that provide the electrons ultimately used in catalysis. In nature, the associated electron transfer sequences can be complicated, energy-inefficient, and rate determining. Here, we employ artificial electron donors, photoexcited semiconductor nanocrystals, to provide the electrons for catalysis. We couple these nanocrystals with an enzyme that catalyzes the formation of carbon−carbon bonds via CO2 reduction. With this architecture, we demonstrate light-driven formation of 2-oxoglutarate, storing some of the photon energy in the chemical product. We examine the role of electron transfer from the nanocrystal to the enzyme in the light-driven chemical conversion and learn that the enzyme modulates this process during catalysis. Redox enzymes are capable of catalyzing a vast array of useful reactions, but they require redox partners that donate or accept electrons. Semiconductor nanocrystals provide a mechanism to convert absorbed photon energy into redox equivalents for enzyme catalysis. Here, we describe a system for photochemical carbon−carbon bond formation to make 2-oxoglutarate by coupling CO2 with a succinyl group. Photoexcited electrons from cadmium sulfide nanorods (CdS NRs) transfer to 2-oxoglutarate:ferredoxin oxidoreductase from Magnetococcus marinus MC-1 (MmOGOR), which catalyzes a carbon−carbon bond formation reaction. We thereby decouple MmOGOR from its native role in the reductive tricarboxylic acid cycle and drive it directly with light. We examine the dependence of 2-oxoglutarate formation on a variety of factors and, using ultrafast transient absorption spectroscopy, elucidate the critical role of electron transfer (ET) from CdS NRs to MmOGOR. We find that the efficiency of this ET depends strongly on whether the succinyl CoA (SCoA) cosubstrate is bound at the MmOGOR active site. We hypothesize that the conformational changes due to SCoA binding impact the CdS NR−MmOGOR interaction in a manner that decreases ET efficiency compared to the enzyme with no cosubstrate bound. Our work reveals structural considerations for the nano−bio interfaces involved in light-driven enzyme catalysis and points to the competing factors of enzyme catalysis and ET efficiency that may arise when complex enzyme reactions are driven by artificial light absorbers.
GC content shapes mRNA storage and decay in human cells

mRNA translation and decay appear often intimately linked although the rules of this interplay are poorly understood. In this study, we combined our recent P-body transcriptome with transcriptomes obtained following silencing of broadly acting mRNA decay and repression factors, and with available CLIP and related data. This revealed the central role of GC content in mRNA fate, in terms of P-body localization, mRNA translation and mRNA stability: P-bodies contain mostly AU-rich mRNAs, which have a particular codon usage associated with a low protein yield; AU-rich and GC-rich transcripts tend to follow distinct decay pathways; and the targets of sequence-specific RBPs and miRNAs are also biased in terms of GC content. Altogether, these results suggest an integrated view of post-transcriptional control in human cells where most translation regulation is dedicated to inefficiently translated AU-rich mRNAs, whereas control at the level of 5’ decay applies to optimally translated GC-rich mRNAs.
Morphological updates and molecular description of Heterosentis holospinus Amin, Heckmann, & Ha, 2011 (Acanthocephala, Arhythmacanthidae) in the Pacific Ocean off Vietnam

Heterosentis holospinus Amin, Heckmann & Ha, 2011 (Arhythmacanthidae) was first described from the striped eel catfish, Plotosus lineatus (Plotosidae) in Halong Bay, Vietnam. New morphological information, scanning electron microscope images, molecular analysis, and Energy Dispersive X-ray analysis (EDXA) of hooks of specimens of H. holospinus from a new collection from the common ponyfish, Leiognathus equulus (Leiognathidae), in Quang Binh, Gulf of Tonkin, Vietnam are reported here for the first time. Additional details of the anterior trunk cone, proboscis hooks, wholly spined trunk, duck-bill-like spines with micropores, and micropore distribution, are described. The unique metal composition of hooks (EDXA) demonstrated a considerably higher level of calcium and phosphorus but lower level of sulfur at the hook basal arch than at the hook tip and edge. An analysis of our new sequences of cytochrome oxidase 1 (COI) showed that H. holospinus had low genetic variation and two haplotypes.
A simple linear readout of MT supports motion direction-discrimination performance.

Motion discrimination is a well-established model system for investigating how sensory signals are used to form perceptual decisions. Classic studies relating single-neuron activity in the middle temporal (MT) area to perceptual decisions have suggested that a simple linear readout could underlie motion discrimination behavior. A theoretically-optimal readout, in contrast, would take into account the correlations between neurons, and the sensitivity of individual neurons at each time point. However, it remains unknown how sophisticated the readout needs to be to support psychophysical motion discrimination or to approach optimal performance. Here, we compare the performance of various neurally-plausible decoders, trained to discriminate motion direction from small ensembles of simultaneously recorded MT neurons, with reference to the psychophysical performance of the animal. We found that decoding the stimulus without knowledge of the inter-neuronal correlations was sufficient to match an optimal (correlation-aware) decoder. Additionally, a decoder could match the psychophysical performance of the animals with at integration of up to half the stimulus and inherited temporal dynamics from the time-varying MT responses. These results demonstrate that simple, linear decoders operating upon small ensembles of neurons can match psychophysical (and optimal) sensitivity without taking correlations into account, and that such simple readout mechanisms can exhibit complex temporal properties inherited from the sensory dynamics themselves.
[Pollution Characteristics and Source Apportionment of Fine Particulate Matter in Autumn and Winter in Puyang, China].

As one of the air pollution transmission channels around the beijing-Tianjin-Hebei region, Puyang frequently suffer from severe airpollution in autumn and winter. In order to study the characteristics and main sources of fine particulate matter during these periods, manual membrane sampling of PM2.5 was conducted at three national control sites from October 15, 2017, to January 13, 2018. Chemical composition analysis was conducted and, combined with a PMF receptor model, source analysis of the fine particles was also undertaken. The results show that the average mass concentration of PM2.5 in Puyang was 94.16 μg·m-3 in the autumn and winter of 2017, and Pushuihe station was the most polluted site. During the heating season, the three control stations all recorded the frequent occurrence of severe and serious pollution events, while the frequency of mild pollution events decreased. When heavy pollution events occurred, the concentrations of NO2 and CO increased significantly. The main components of PM2.5 were water-soluble ions (52.33%), OCEC (25.32%), and crustal elements (0.08%). The concentrations of NO3- were high while the concentrations of SO42- were low. When heavy pollution occurred, the concentrations of water-soluble ions, OC, EC, and K in PM2.5 increased significantly, while the concentrations of crustal elements decreased. During the sampling period, the conversion ratios of sulfur and nitrogen in Puyang were high and atmospheric oxidation was strong. The transformation of sulfur and nitrogen promoted the occurrence of heavy pollution. Emissions of NOx, CO, and VOCs were higher in Puyang in 2017, and the source apportionment results showed that the main sources of PM2.5 in autumn and winter were secondary inorganic salts (37%), industrial sources (16%), secondary organic aerosol (SOA, 14%), biomass combustion (12%), mobile sources (9%), coal burning (7%), and dust (4%). Secondary transformation played an important role in the development of heavy pollution events in Puyang. It is necessary to focus on the control of emissions from industrial sources, biomass combustion, moving source, and civil coal combustion.
Vitamin A Deficiency in Patients Undergoing Sleeve Gastrectomy and Gastric Bypass: A 2-Year, Single-Center Review.

Introduction: Vitamin A deficiency (VAD) is an underreported micronutrient deficiency after bariatric surgery (BS). Objectives: The goal of this study was to characterize VAD prevalence in patients undergoing malabsorptive and restrictive procedures up to 2 years postoperatively. Methods: Primary sleeve gastrectomy (SG; n = 322) and gastric bypass (GB; n = 249) patients were reviewed. Levels for overall VAD (oVAD; retinol <39 mcg/dL) and moderate VAD (mVAD; retinol <30 mcg/dL) were reported preoperatively and 6, 12, and 24 months postoperatively. Differences in demographic, surgical, and postoperative data were tested between these groups. Settings: Single-center academic institution. Results: Serum retinol levels were documented for 56%, 74%, 61%, and 37% of patients for listed time points. Baseline retinol inversely correlated to preop body mass index (BMI) (R = -0.15, P = .007). Both oVAD and mVAD peaked 6 months postoperatively (33% vs. 15%, P < .005; 12% vs. 4%, P = .0004, respectively). oVAD remained elevated at 24 months (22% vs. 15%, P = .03). Compared to SG, oVAD was higher following GB at 6 months (39% vs. 28%, P = .001) and 12 months (26% vs. 17%, P = .04), and mVAD was greater with GB at 6 months (18% vs. 6%, P < .0005). African American patients had higher oVAD/mVAD preoperatively (26% vs. 13%, P = .02; 13% vs. 3%, P = .001, respectively) and at 6 months (19% vs. 10%, P = .04). Prior mild VAD (retinol 1.05-1.35 μM) was significantly associated with mVAD up to 12 months postoperatively. Conclusions: Although higher following LRYGB, VAD is prevalent following both malabsorptive and restrictive procedures. Preoperative serum retinol is inversely correlated to increasing BMI, and African American race and mild VAD are associated with moderate VAD.