Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcomes of laparoscopic repeat liver resection for recurrent liver cancer

Abstract Background: With the improvements of surgical instruments and surgeons’ experience, laparoscopic liver resection has been applied for recurrent tumors. However, the value of laparoscopic repeat liver resection (LRLR) is still controversial nowadays, which compelled us to conduct this meta-analysis to provide a comprehensive evidence about the efficacy of LRLR for recurrent liver cancer. Methods: A computerized search was performed to identify all eligible trials published up to April 2019. This meta-analysis was conducted to estimate the perioperative data and oncological outcomes of LRLR by compared with open repeat liver resection (ORLR) and laparoscopic primary liver resection (LPLR). A fixed or random-effect modal was established to collect the data. Results: A total of 1232 patients were included in this meta-analysis (LRLR: n = 364; ORLR: n = 396; LPLR: n = 472). LRLR did not increase the operative time compared to ORLR (WMD = 15.92 min; 95%CI: −33.53 to 65.37; P = .53). Conversely, LRLR for patients with recurrent tumors was associated with less intraoperative blood loss (WMD = −187.33 mL; 95%CI: −249.62 to −125.02; P < .00001), lower transfusion requirement (OR = 0.24; 95%CI: 0.06–1.03; P = .05), fewer major complications (OR = 0.42; 95%CI: 0.23–0.76; P = .004), and shorter hospital stays (WMD = −2.31; 95%CI: −3.55 to −1.07; P = .0003). In addition, the oncological outcomes were comparable between the two groups. However, as for the safety of LRLR compared with LPLR, although the operative time in LRLR group was longer than LPLR group (WMD = 58.63 min; 95%CI: 2.99–114.27; P = .04), the blood loss, transfusion rates, R0 resection, conversion, postoperative complications, and mortality were similar between the two groups. Conclusions: LRLR for recurrent liver cancer could be safe and feasible in selected patients when performed by experienced surgeons.
Development and Application of a Life-Stage Physiologically Based Pharmacokinetic (PBPK) Model to the Assessment of Internal Dose of Pyrethroids in Humans

Abstract To address concerns around age-related sensitivity to pyrethroids, a life-stage physiologically based pharmacokinetic (PBPK) model, supported by in vitro to in vivo extrapolation (IVIVE) was developed. The model was used to predict age-dependent changes in target tissue exposure of 8 pyrethroids; deltamethrin (DLM), cis-permethrin (CPM), trans-permethrin, esfenvalerate, cyphenothrin, cyhalothrin, cyfluthrin, and bifenthrin. A single model structure was used based on previous work in the rat. Intrinsic clearance (CLint) of each individual cytochrome P450 or carboxylesterase (CES) enzyme that are active for a given pyrethroid were measured in vitro, then biologically scaled to obtain in vivo age-specific total hepatic CLint. These IVIVE results indicate that, except for bifenthrin, CES enzymes are largely responsible for human hepatic metabolism (>50% contribution). Given the high efficiency and rapid maturation of CESs, clearance of the pyrethroids is very efficient across ages, leading to a blood flow-limited metabolism. Together with age-specific physiological parameters, in particular liver blood flow, the efficient metabolic clearance of pyrethroids across ages results in comparable to or even lower internal exposure in the target tissue (brain) in children than that in adults in response to the same level of exposure to a given pyrethroid (Cmax ratio in brain between 1- and 25-year old = 0.69, 0.93, and 0.94 for DLM, bifenthrin, and CPM, respectively). Our study demonstrated that a life-stage PBPK modeling approach, coupled with IVIVE, provides a robust framework for evaluating age-related differences in pharmacokinetics and internal target tissue exposure in humans for the pyrethroid class of chemicals.
Clinical impact of the cell-of-origin classification based on immunohistochemistry criteria and Lymph2Cx of diffuse large B-Cell lymphoma patients in a South-east Asian population: a single center experience and review of the literature

ABSTRACT Background: Previous studies in Western populations, using immunohistochemistry (IHC) methods to subtype diffuse large B-cell lymphoma (DLBCL), suggest that germinal center B-cell lymphomas (GCBs) have improved outcomes. However, data in Asians have been limited and conflicting. This study aims to evaluate the prognostic impact of cell-of-origin (COO) subtyping by IHC and Lymph2Cx in South-East Asian (SEA) DLBCL patients, and to summarize the existing literature. Methods: A single-center retrospective analysis of 384 DLBCL patients diagnosed 2013–2018 who received Rituximab-based chemotherapy was performed. Hans and Lymph2Cx were used to assign COO and correlated with outcomes. Results: International Prognostic Index (IPI) score was associated with overall survival (OS) and progression-free survival (PFS). The 5-yr-OS for non-GCB versus GCB for COO by Hans was 70% versus 71% p=0.39, while 5-yr-OS for ABC versus GCB for COO by Lymph2Cx was 74% versus 92% p=0.19. The 5-yr-PFS for non-GCB versus GCB for COO by Hans was 65% versus 70% p=0.26, while 5-yr-PFS for ABC versus GCB for COO by Lymph2Cx was 64% versus 86% p=0.07. Conclusions: IPI is reaffirmed to be relevant in the rituximab era. COO by Hans has no prognostic significance, while subtyping by Lymph2Cx trends toward GCBs having better PFS and OS.
Impact of Surgical Resection on Survival Outcomes After Chemoradiotherapy in Anal Adenocarcinoma.

BACKGROUND Anal adenocarcinoma is a rare malignancy with a poor prognosis, and no randomized data are available to guide management. Prior retrospective analyses offer differing conclusions on the benefit of surgical resection after chemoradiotherapy (CRT) in these patients. We used the National Cancer Database (NCDB) to analyze survival outcomes in patients undergoing CRT with and without subsequent surgical resection. METHODS Patients with adenocarcinoma of the anus diagnosed in 2004 through 2015 were identified using the NCDB. Patients with metastatic disease and survival <90 days were excluded. We analyzed patients receiving CRT and stratified by receipt of surgical resection. Logistic regression was used to evaluate predictors of use of surgery and to form a propensity score-matched cohort. Overall survival (OS) was compared between treatment strategies using Cox proportional hazards regression. RESULTS We identified 1,747 patients with anal adenocarcinoma receiving CRT, of whom 1,005 (58%) received surgery. Predictors of increased receipt of surgery included age <65 years, private insurance, overlapping involvement of the anus and rectum, N0 disease, and external-beam radiation dose ≥4,000 cGy. With a median follow-up of 3.5 years, 5-year OS was 61.1% in patients receiving CRT plus surgery compared with 39.8% in patients receiving CRT alone (log-rank P<.001). In multivariate analysis, surgery was associated with significantly improved OS (hazard ratio, -0.59; 95% CI, 0.50-0.68; P<.001). This survival benefit persisted in a propensity score-matched cohort (log-rank P<.001). CONCLUSIONS In the largest series of anal adenocarcinoma cases to date, treatment with CRT followed by surgery was associated with a significant survival benefit compared with CRT alone in propensity score-matching analysis. Our findings support national guideline recommendations of neoadjuvant CRT followed by resection for patients with anal adenocarcinoma.
Identifying Clouds With Convolutional Neural Networks

The greatest source of uncertainty in model estimates of projected climate change involve clouds and aerosols [1]. Photographic images of clouds in the sky are simple to acquire and archive, but climate scientists need an automated process for identifying clouds in these images. We bring machine learning to bear on this problem. Specifically, we use convolutional neural networks [2], which to our knowledge have not previously been applied to this task [3]. We trained a network to identify clear sky, thin cloud, thick cloud, and non-sky pixels in photos taken by the Total Sky Imager [4]. The trained network is capable of classifying 91.9% of pixels correctly. An ensemble of several networks increases this to 94.6%. Results Future Work The Total Sky Imager (TSI) consists of a downward facing digital camera directed at an upward facing convex mirror to produce photographs of the sky [4]. The TSI takes a picture every 30 seconds, so millions of images are available [5]. Several TSI devices are in use around the world; we draw our data from a climate research facility in Oklahoma. We use 467,906 pictures taken from January to November of 2006. A convolutional neural network learns to recognize patterns by generalizing from many examples. Such networks have been very successful in artificial vision tasks [2]. The network consists of a series of layers, each of which computes a modified version of the output of the previous layer. The first layer takes the image as input. Convolutional Neural Networks
Management Strategies for Antidepressant-Related Sexual Dysfunction: A Clinical Approach

Major depressive disorder is a serious mental disorder in which treatment with antidepressant medication is often associated with sexual dysfunction (SD). Given its intimate nature, treatment emergent sexual dysfunction (TESD) has a low rate of spontaneous reports by patients, and this side effect therefore remains underestimated in clinical practice and in technical data sheets for antidepressants. Moreover, the issue of TESD is rarely routinely approached by clinicians in daily praxis. TESD is a determinant for tolerability, since this dysfunction often leads to a state of patient distress (or the distress of their partner) in the sexually active population, which is one of the most frequent reasons for lack of adherence and treatment drop-outs in antidepressant use. There is a delicate balance between prescribing an effective drug that improves depressive symptomatology and also has a minimum impact on sexuality. In this paper, we detail some management strategies for TESD from a clinical perspective, ranging from prevention (carefully choosing an antidepressant with a low rate of TESD) to possible pharmacological interventions aimed at improving patients’ tolerability when TESD is present. The suggested recommendations include the following: for low sexual desire, switching to a non-serotoninergic drug, lowering the dose, or associating bupropion or aripiprazole; for unwanted orgasm delayal or anorgasmia, dose reduction, “weekend holiday”, or switching to a non-serotoninergic drug or fluvoxamine; for erectile dysfunction, switching to a non-serotoninergic drug or the addition of an antidote such as phosphodiesterase 5 inhibitors (PD5-I); and for lubrication difficulties, switching to a non-serotoninergic drug, dose reduction, or using vaginal lubricants. A psychoeducational and psychotherapeutic approach should always be considered in cases with poorly tolerated sexual dysfunction.
Stereotyped transcriptomic transformation of somatosensory neurons in response to injury

In mice, spared nerve injury replicates symptoms of human neuropathic pain and induces upregulation of many genes in somatosensory neurons. Here we used single cell transcriptomics to probe the effects of partial infraorbital transection of the trigeminal nerve at the cellular level. Uninjured neurons were unaffected by transection of major nerve branches, segregating into many different classes. In marked contrast, axotomy rapidly transformed damaged neurons into just two new and closely-related classes where almost all original identity was lost. Remarkably, sensory neurons also adopted this transcriptomic state following various minor peripheral injuries. By genetically marking injured neurons, we showed that the injury-induced transformation was reversible, with damaged cells slowly reacquiring normal gene expression profiles. Thus, our data expose transcriptomic plasticity, previously thought of as a driver of chronic pain, as a programed response to many types of injury and a potential mechanism for regulating sensation during wound healing.
Root induced soil deformation influences Fe, S and P: rhizosphere chemistry investigated using synchrotron XRF and XAS.

Rhizosphere soil has distinct physical and chemical properties from bulk soil. However, besides root induced physical changes, chemical changes have not been extensively measured in situ on the pore scale. In this study we couple structural information, previously obtained using synchrotron X-ray computed tomography (XCT), with synchrotron X-ray Fluorescence (SR-XRF) microscopy and X-ray Absorption Near-Edge Structure (XANES) to unravel chemical changes induced by plant roots. Our results suggest that iron (Fe) and sulfur (S) increase notably in the direct vicinity of the root via solubilization and microbial activity. XANES further shows that Fe is slightly reduced, S is increasingly transformed into sulfate (SO4 2- ) and that phosphorus (P) is increasable adsorbed to humic substances in this enrichment zone. In addition, the ferrihydrite fraction decreases drastically suggesting the preferential dissolution and the formation of more stable Fe-oxides. Additionally, the increased transformation of organic S to sulfate indicates that the microbial activity in this zone is increased. These changes in soil chemistry correspond to the soil compaction zone as previously measured via X-ray CT. The fact that these changes are co-located near the root and the compaction zone suggests that decreased permeability due to soil structural changes acts as a barrier creating a zone with increased rhizosphere chemical interactions via surface mediated processes, microbial activity and acidification.
Highly Sensitive and Rapid Characterization of the Development of Synchronized Blood Stage Malaria Parasites Via Magneto-Optical Hemozoin Quantification

The rotating-crystal magneto-optical diagnostic (RMOD) technique was developed as a sensitive and rapid platform for malaria diagnosis. Herein, we report a detailed in vivo assessment of the synchronized Plasmodium vinckei lentum strain blood-stage infections by the RMOD method and comparing the results to the unsynchronized Plasmodium yoelii 17X-NL (non-lethal) infections. Furthermore, we assess the hemozoin production and clearance dynamics in chloroquine-treated compared to untreated self-resolving infections by RMOD. The findings of the study suggest that the RMOD signal is directly proportional to the hemozoin content and closely follows the actual parasitemia level. The lack of long-term accumulation of hemozoin in peripheral blood implies a dynamic equilibrium between the hemozoin production rate of the parasites and the immune system’s clearing mechanism. Using parasites with synchronous blood stage cycle, which resemble human malaria parasite infections with Plasmodium falciparum and Plasmodium vivax, we are demonstrating that the RMOD detects both hemozoin production and clearance rates with high sensitivity and temporal resolution. Thus, RMOD technique offers a quantitative tool to follow the maturation of the malaria parasites even on sub-cycle timescales.
Head-to-head drug comparisons in multiple sclerosis

Disease-modifying drugs are changing the natural history of multiple sclerosis (MS). However, currently available clinical trial data are insufficient to develop accurate personalized treatment algorithms to assign the best possible treatment to each person with MS according to disease features, treatment history, and comorbidities. Such accurate algorithms would require the presence of numerous head-to-head trials of long duration, which is virtually impossible, given the economic costs, required time, and difficulties with attrition. Thus, efforts are being made to compare relative treatment efficacy through observational designs, using large multicenter prospective cohorts or “big MS data,” and network meta-analyses. Although such studies can yield useful information, they are liable to biases and their results should be confirmed in other study populations, including smaller, single-center cohorts, where some of these biases can be minimized. In this View article, we analyze the potential benefits and biases of all these strategies alternative to head-to-head trials in MS. Finally, we propose the combination of all these types of studies to obtain reliable head-to-head drug comparisons in the absence of randomized designs.
Solvent-Free C-3 Coupling of Azaindoles with Cyclic Imines

By direct coupling 7-azaindole and cyclic imines, such as 3,4-dihydroisoquinoline, 6,7-dihydrothieno[3,2-c]pyridine, 3,4-dihydro-β-carboline, and 4,5-dihydro-3H-benz[c]azepine, new 3-substituted 7-azaindole derivatives have been synthesized. The reaction was extended to 4-azaindoles and 6-azaindoles, as electron-rich aromatic compounds. The lowest reactivity was observed in the case of C-3 substitution of 5-azaindole. In this case, the aza-Friedel-Crafts reaction took place by using 10 mol % of p-toluenesulfonic acid (p-TSA) as the catalyst. The role of the acid catalyst can be explained by the different pKa values of the azaindoles. All reactions were performed in solvent-free conditions by using both classical heating and microwave irradiation. In all cases, microwave heating proved to be more convenient to synthesize new C-3-substituted azaindole derivatives.
RETRACTED ARTICLE: Long non-coding RNA SNHG4 promotes cervical cancer progression through regulating c-Met via targeting miR-148a-3p

ABSTRACT We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Hanchen Li, Jiang Hong and Walimuni Sandaroo Mendis Abeysekara Wijayakulathilaka. Long non-coding RNA SNHG4 promotes cervical cancer progression through regulating c-Met via targeting miR-148a-3p. Cell Cycle. 2019;18(23):3313-3324. doi: 10.1080/15384101.2019. 1674071 Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
Attributes of Perceived Bikeability in a Compact Urban Neighborhood Based on Qualitative Multi-Methods

Cycling provides opportunities to promote healthy and sustainable cities. However, few studies examine cyclists’ perceived attributes of a bicycle-friendly environment in relation to compact urban contexts. This study explored the attributes of perceived bikeability and urban context related to the cycling experience in Seoul, Korea. Purposive sampling with public recruitment and a snowball technique was used to recruit twenty-two cyclists and three bicycle-related community service providers from a bikeable environment. Qualitative multi-methods, including semi-structured interviews and bicycle tours with a GPS device, were adopted. The main themes of perceived bikeability were derived through thematic analysis. Cyclists perceived the attributes of a bicycle-friendly physical environment as essential components of bikeability. In urban environments where cycling is not yet recognized as the main transportation mode, internal conflict among cyclists and external conflicts between cyclists and other transportation users were evident. A supportive community system included developing an appropriate environment, providing information, and expanding riding opportunities. A bicycle-friendly culture accumulated over a long period influenced the initiation and maintenance of cycling and contributed to a more bikeable community environment. Cyclists’ attitude, behaviors, and perceived environment differed according to purpose. Policy, system, and environmental changes are required to promote cycling in compact urban contexts.
Outcome of endovascular therapy in stroke with large vessel occlusion and mild symptoms

Objective To compare outcomes after endovascular therapy (EVT) and IV thrombolysis (IVT) in patients with stroke with emergent large vessel occlusion (LVO) and mild neurologic deficits. Methods This was a retrospective analysis of patients from the Swiss Stroke Registry with admission NIH Stroke Scale score ≤5 and LVO treated by EVT (± IVT) vs IVT alone. The primary endpoint was favorable functional outcome (modified Rankin Scale [mRS] score 0–1) at 3 months. Secondary outcomes were independence (mRS score 0–2), mRS score (ordinal shift analysis), and survival with high disability (mRS score 4–5). Safety endpoints were mortality and symptomatic hemorrhage. Results Of 11,356 patients, 312 met the criteria and propensity score method matched 108 in each group. A comparably large proportion of patients with EVT and IVT had favorable outcome (63% vs 65.7% respectively; odds ratio 0.94, 95% confidence interval 0.51–1.72; p = 0.840). Patients with EVT showed a nonsignificant trend toward higher mRS score at 3 months (p = 0.717), while the proportion of surviving patients with high disability was comparably very low in both groups (p = 0.419). Mortality was slightly higher among those with EVT (9.3% vs 2.8%; p = 0.06), and symptomatic intracranial hemorrhage was a rare event in both groups (2.8% vs 0%; p = 0.997). Conclusions In acute ischemic stroke, EVT and IVT appear similarly effective in achieving favorable outcome at 3 months for patients with LVO and mild neurologic symptoms. EVT might be marginally inferior to IVT regarding outcome across all levels of disability and mortality. Further studies are required to determine whether certain subgroups of patients with LVO and mild symptoms benefit from EVT. Classification of evidence This study provides Class III evidence that patients with LVO and mild symptoms receiving either EVT or IVT had similar favorable functional outcomes at 3 months.
Microbial Interactions in Oral Communities Mediate Emergent Biofilm Properties

Oral microbial communities are extraordinarily complex in taxonomic composition and comprise interdependent biological systems. The bacteria, archaea, fungi, and viruses that thrive within these communities engage in extensive cell-cell interactions, which are both beneficial and antagonistic. Direct physical interactions among individual cells mediate large-scale architectural biofilm arrangements and provide spatial proximity for chemical communication and metabolic cooperation. In this review, we summarize recent work in identifying specific molecular components that mediate cell-cell interactions and describe metabolic interactions, such as cross-feeding and exchange of electron acceptors and small molecules, that modify the growth and virulence of individual species. We argue, however, that although pairwise interaction models have provided useful information, complex community-like systems are needed to study the properties of oral communities. The networks of multiple synergistic and antagonistic interactions within oral biofilms give rise to the emergent properties of persistence, stability, and long-range spatial structure, with these properties mediating the dysbiotic transitions from health to oral diseases. A better understanding of the fundamental properties of interspecies networks will lead to the development of effective strategies to manipulate oral communities.