Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Smoking and Primary Tumor Subsite on Recurrence in HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Objective To describe risk of recurrence and recurrence characteristics between ever- and never-smoking patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) when stratified by primary tumor subsite. Study Design Retrospective observational study. Setting Tertiary care center. Methods Retrospective chart review of 171 patients with HPV+ OPSCC with primary treatment between 2008 and 2019. Five-year recurrence-free survival and risk of recurrence were evaluated through Kaplan-Meier curves with log-rank test and Cox proportional hazards models, respectively. Results Of 171 patients with HPV+ OPSCC, 81.9% were male, and the average age was 63.9 years. Eighty patients (46.8%) had a smoking history (average, 17.7 pack-years), including 4 current smokers. Recurrence occurred in 31 patients (18.1%), 19 of whom were ever smokers. The recurrence rate for ever smokers with primary base of tongue (BOT) cancer was 41.7%, while 5.1% of never smokers with BOT primaries had recurrence. For primary tonsillar disease, 9.1% of ever smokers had recurrence versus 19.2% of never smokers. Five-year recurrence-free survival for BOT primaries was lower in ever smokers than never smokers (P = .001) but did not differ between ever and never smokers for tonsillar primaries (P = .215). In multivariable analysis across this period, ever-smoking status was associated with higher risk of recurrence than never-smoking status in BOT primaries (adjusted hazard ratio, 7.36; 95% CI, 1.61-33.68; P = .010) but with lower risk of recurrence after tonsillar primaries (adjusted hazard ratio, 0.23; 95% CI, 0.06-0.89; P = .033). Conclusion Smoking may uniquely interact with tumor subsites within the oropharynx to influence recurrence risk. Understanding the association between smoking and HPV+ OPSCC recurrence could lead to personalized, evidence-based treatments to improve oncologic outcomes.
Urinary metabolomics analysis of the protective effects of Daming capsule on hyperlipidemia rats using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

Hyperlipidemia is recognized as one of the most important risk factors for morbidity and mortality due to cardiovascular diseases. Daming capsule, a Chinese patent medicine, has shown definitive efficacy in patients with hyperlipidemia. In this study, serum biochemistry and histopathology assessment were used to investigate the lipid-lowering effect of Daming capsule. Furthermore, urinary metabolomics based on ultra-HPLC with quadrupole TOF MS was conducted to identify the urinary biomarkers associated with hyperlipidemia and discover the underlying mechanisms of the anti-hyperlipidemic action of Daming capsule. After 10 weeks of treatment, Daming capsule significantly lowered serum lipid levels and ameliorated hepatic steatosis induced by a high-fat diet. A total of 33 potential biomarkers associated with hyperlipidemia were identified, among which 26 were robustly restored to normal levels after administration of Daming capsule. Pathway analysis revealed that the lipid-lowering effect of Daming capsule is related to the regulation of multiple metabolic pathways, including vitamin B and amino acid metabolism, tricarboxylic acid cycle, and pentose phosphate pathway. Notably, the study demonstrates that metabolomics is a powerful tool to elucidate the multi-target mechanism of traditional Chinese medicines, thereby promoting their research and development. This article is protected by copyright. All rights reserved.
Second-order multi-instance learning model for whole slide image classification

Whole slide histopathology images (WSIs) play a crucial role in diagnosing lymph node metastasis of breast cancer, which usually lack fine-grade annotations of tumor regions and have large resolutions (typically 105 × 105 pixels). Multi-instance learning has gradually become a dominant weakly supervised learning framework for WSI classification when only slide-level labels are available. In this paper, we develop a novel second-order multiple instances learning method (SoMIL) with an adaptive aggregator stacked by the attention mechanism and recurrent neural network (RNN) for histopathological image classification. To be specific, the proposed method applies a second-order pooling module (matrix power normalization covariance) for instance-level feature extraction of weakly supervised learning framework, attempting to explore second-order statistics of deep features for histopathological images. Additionally, we utilize an efficient channel attention mechanism to adaptively highlight the most discriminative instance features, followed by an RNN to update the final bag-level representation for the slide classification. Experimental results on the lymph node metastasis dataset of 2016 Camelyon grand challenge demonstrate the significant improvement of our proposed SoMIL framework compared with other state-of-the-art multi-instance learning methods. Moreover, in the external validation on 130 WSIs, SoMIL also achieves an impressive area under the curve performance that competitive to the fully-supervised framework.
Predicted N‐terminal N‐linked glycosylation sites may underlie membrane protein expression patterns in Saccharomyces cerevisiae

N‐linked glycosylation is one type of posttranslational modification that proteins undergo during expression. The following describes the effects of N‐linked glycosylation on high‐level membrane protein expression in yeast with an emphasis on Saccharomyces cerevisiae. N‐linked glycosylation is highlighted here as an important consideration when preparing membrane protein gene constructs for expression in S. cerevisiae, which continues to be used as a workhorse in both research and industrial applications. Non‐native N‐linked glycosylation commonly occurs during the heterologous expression of mammalian proteins in many yeast species which can have important immunological consequences when used in the production of biotherapeutic proteins or peptides. Further, non‐native N‐linked glycosylation can lead to improper protein folding and premature degradation, which can impede high‐level expression yields and hinder downstream analysis. Multiple strategies are presented in this article, which suggest different methods that can be implemented to circumvent the unwanted consequences of N‐linked glycosylation during the expression process. These considerations may have long‐term benefits for high‐level protein production in S. cerevisiae across a broad spectrum of expression targets with special emphasis placed on G‐protein coupled receptors, one of the largest families of membrane proteins.
Atomistic Simulations of the Surface Coverage of Large Gold Nanocrystals

Here, the adsorption of alkanethiols (from ethane to dodecanethiol) on icosahedral gold nanocrystals with diameters up to 10 nm is studied by molecular dynamics simulations in a vacuum. The surface coverage of the nanocrystals obtained in the simulations is in good agreement with experimental data. We show that the average surface per adsorbed thiol does not markedly depend on the nanocrystal size and ligand and is only about 10% lower than the value observed on a flat Au(111) surface. We observe two different molecular organizations of the thiolates on the edges and in the centers of the nanocrystal facets. The incompatibility between both organizations explains the fact that the formation of self-assembled monolayers usually observed on flat Au(111) surfaces is hindered for nanocrystals smaller than 6 nm. We also show that the organization of thiolates on the edges is at the origin of the lower average surface per adsorbed thiol found for the nanocrystal.
A prospective examination of COVID‐19‐related social distancing practices on suicidal ideation

Abstract Background The COVID‐19 pandemic has spurred the implementation of several public safety measures to contain virus spread, most notably socially distancing policies. Prior research has linked similar public safety measures (i.e., quarantine) with suicide risk, in addition to supporting the role of social connection in suicidal thoughts and behaviors; consequently, there is a need to better understand the relationship between widespread social distancing policies and suicide risk. The current study aimed to examine the prospective association between COVID‐19‐related social distancing practices and suicidal ideation. Methods Participants (N = 472) completed measures of suicidal ideation and impacts of social distancing practices at baseline and two weeks later. Results After controlling for general psychosocial distress (i.e., depression, social connectedness), cross‐lagged regression models identified prospective, bidirectional relationships between perceived impacts of social distancing on one's mental health and both passive and active suicidal ideation. The impact of social distancing on work/social routine was not associated with suicidal ideation. Conclusions Overall, findings suggest the importance of an individual's perception regarding the effect of social distancing on their mental health, rather than the disruption to work or social routine, in suicide risk. Findings highlight potential targets for suicide risk prevention and intervention.
Predicting risk along the suicidality continuum: A longitudinal, nationally representative study of the Irish population during the COVID‐19 pandemic

Abstract Introduction Little is known about the lifetime prevalence of different indicators of suicidality in the Irish general population; whether suicidality has increased during the COVID‐19 pandemic; and what factors associated with belonging to different points on a continuum of suicidality risk. Methods A nationally representative sample of Irish adults (N = 1,032) completed self‐report measures in May 2020 and a follow‐up in August 2020 (n = 715). Results Lifetime prevalence rates were 29.5% for suicidal ideation, 12.9% for non‐suicidal self‐injury (NSSI), and 11.2% for attempted suicide. There were no changes in past two‐week rates of NSSI and attempted suicide during the pandemic. Correlations between the indicators of suicidality supported a progression from ideation to NSSI to attempted suicide. Suicidal ideation alone was associated with being male, unemployed, higher loneliness, and lower religiosity. NSSI (with no co‐occurring attempted suicide) was associated with a history of mental health treatment. Attempted suicide was associated with ethnic minority status, lower education, lower income, PTSD, depression, and history of mental health treatment. Conclusion Suicidal ideation, NSSI, and attempted suicide are relatively common phenomena in the general adult Irish population, and each has unique psychosocial correlates. These findings highlight important targets for prevention and intervention efforts.
Activated neutrophils polarize protumorigenic interleukin‐17A‐producing T helper subsets through TNF‐α‐B7‐H2‐dependent pathway in human gastric cancer

Abstract Rationale Neutrophils constitute massive cellular constituents in inflammatory human gastric cancer (GC) tissues, but their roles in pathogenesis of inflammatory T helper (Th) subsets are still unknown. Methods Flow cytometry analysis and immunohistochemistry were used to analyze the responses and phenotypes of neutrophils in different samples from 51 patients with GC. Kaplan‐Meier plots and Multivariate analysis for the survival of patients were used by log‐rank tests and Cox proportional hazards models. Neutrophils and CD4+ T cells were purified and cultured for ex vivo, in vitro and in vivo regulation and function assays. Results GC patients exhibited increased tumoral neutrophil infiltration with GC progression and poor patient prognosis. Intratumoral neutrophils accumulated in GC tumors via CXCL6/CXCL8‐CXCR1‐mediated chemotaxis, and expressed activated molecule CD54 and co‐signaling molecule B7‐H2. Neutrophils induced by tumors strongly expressed CD54 and B7‐H2 in both dose‐ and time‐dependent manners, and a close correlation was obtained between the expressions of CD54 and B7‐H2 on intratumoral neutrophils. Tumor‐derived tumor necrosis factor‐α (TNF‐α) promoted neutrophil activation and neutrophil B7‐H2 expression through ERK‐NF‐κB pathway, and a significant correlation was found between the levels of TNF‐α and CD54+ or B7‐H2+ neutrophils in tumor tissues. Tumor‐infiltrating and tumor‐conditioned neutrophils effectively induced IL‐17A‐producing Th subset polarization through a B7‐H2‐dependent manner ex vivo and these polarized IL‐17A‐producing Th cells exerted protumorigenic roles by promoting GC tumor cell proliferation via inflammatory molecule IL‐17A in vitro, which promoted the progression of human GC in vivo; these effects could be reversed when IL‐17A is blocked. Moreover, increased B7‐H2+ neutrophils and IL‐17A in tumors were closely related to advanced GC progression and predicted poor patient survival. Conclusion We illuminate novel underlying mechanisms that TNF‐α‐activated neutrophils link B7‐H2 to protumorigenic IL‐17A‐producing Th subset polarization in human GC. Blocking this pathological TNF‐α‐B7‐H2‐IL‐17A pathway may be useful therapeutic strategies for treating GC.
Clinical Characteristics of Patients with Persistent Apogeotropic and Persistent Geotropic Direction-Changing Positional Nystagmus

Background and Purpose This study aimed to determine the clinical features, diagnosis, and treatment of patients with persistent geotropic (pG) and persistent apogeotropic (pAG) direction-changing positional nystagmus (DCPN). Methods This retrospective study included 30 patients with pG-DCPN and 44 patients with pAG-DCPN. All patients underwent neurological and neurotological examinations, including an evaluation of gaze-evoked nystagmus, eye-movement tests, and assessments of limb ataxia and balance, as well as magnetic resonance imaging to exclude central causes. The characteristics of positional nystagmus were detected using the supine roll test (SRT) and bow-and-lean test (BLT). The null point (NP) at which the nystagmus disappeared was determined. All patients were treated with the barbecue maneuver, and treatment efficacy was evaluated immediately, 1 week, and 1 month after treatment. Results The history of diseases associated with atherosclerosis, peripheral vestibular disorders, otological disease, and migraine differed significantly between patients with pG-DCPN and pAG-DCPN. The affected sides of persistent horizontal DCPN can be determined using the SRT and the BLT, while determining the second NP and vestibular function as well as performing an audiological evaluation can be used to assist in identifying the affected side. The efficacy rates immediately and 1 week after treatment with the barbecue maneuver were higher in patients with pAG-DCPN than in patients with pG-DCPN. Conclusions pAG-DCPN was more compatible with the characteristics of cupulolithiasis, and pG-DCPN was more likely to be associated with a light cupula rather than canalolithiasis. pAG-DCPN was more likely to be accompanied by a disease associated with atherosclerosis, while pG-DCPN was often accompanied by autoimmune-related diseases and a history of migraine. The associations between pAG-DCPN, pG-DCPN, and the above-mentioned diseases need to be clarified further. The canalith-repositioning maneuver was effective in patients with pAG-DCPN and ineffective in patients with pG-DCPN, but most cases of pG-DCPN are self-limiting.
Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers

Antibody-drug conjugates represent a new class of highly potent antineoplastic drugs built by attaching a small molecule of an anticancer drug (payload) or another therapeutic agent to an antibody recognizing an epitope on the targeted cells. Trophoblast cell-surface antigen-2 (Trop-2) was originally described in trophoblasts and fetal tissues, but subsequently its overexpression has been demonstrated in various solid malignancies. Sacituzumab govitecan (SG), a conjugate of anti-Trop-2 antibody and SN-38 payload (an active metabolite of irinotecan), is the first in the class that has been clinically validated and approved by the Food and Drug Administration for the treatment of metastatic triple-negative breast (2020) and urothelial carcinomas (2021). In the current review, we summarize and critically appraise the most recent advances with regard to SG, emphasizing the predictive biomarker analysis.
Heteroleptic, Dinuclear Copper(I) Complexes for Application in Organic Light-Emitting Diodes

A series of highly luminescent, heteroleptic copper(I) complexes has been synthesized using a modular approach based on easily accessible P^N ligands, triphenylphosphine, and copper(I) halides, allowing for an independent tuning of the emission wavelength with low synthetic efforts. The molecular structure has been investigated via X-ray analysis, confirming a dinuclear copper(I) complex consisting of a butterfly shaped metal-halide cluster and two different sets of ligands. The bidentate P^N ligand bridges the two metal centers and can be used to tune the energy of the frontier orbitals and therefore the photophysical characteristics, as confirmed by emission spectroscopy and theoretical investigations, whereas the two monodentate triphenylphosphine ligands on the periphery of the cluster core mainly influence the solubility of the complex. By using electron-rich or electron-poor heterocycles as part of the bridging ligand, emission colors can be adjusted, respectively, between yellow (581 nm) and deep b.
Elimination of fibrin γ-chain cross-linking by FXIIIa increases pulmonary embolism arising from murine inferior vena cava thrombi

Significance Pulmonary embolism and stroke are thromboembolic diseases affecting >1 million people annually worldwide. Thromboembolism involves clot fragments affecting vital downstream organs such as the lung or brain. The mechanisms underpinning thromboembolism are not understood and require clarification in order to devise more effective treatments. Here, we developed a thromboembolism protocol supported by state-of-the-art in vivo imaging, coupled to a genetically modified murine model of reduced clot strength caused by mutations in the cross-linking sites of fibrin, which provides the mechanical scaffold of the clot. We find that fibrin γ-chain cross-linking is essential for clot stability and reduces embolism. These findings introduce an important concept indicating that maintenance of clot stability during thrombosis treatment is essential to prevent thromboembolism. The onset of venous thromboembolism, including pulmonary embolism, represents a significant health burden affecting more than 1 million people annually worldwide. Current treatment options are based on anticoagulation, which is suboptimal for preventing further embolic events. In order to develop better treatments for thromboembolism, we sought to understand the structural and mechanical properties of blood clots and how this influences embolism in vivo. We developed a murine model in which fibrin γ-chain cross-linking by activated Factor XIII is eliminated (FGG3X) and applied methods to study thromboembolism at whole-body and organ levels. We show that FGG3X mice have a normal phenotype, with overall coagulation parameters and platelet aggregation and function largely unaffected, except for total inhibition of fibrin γ-chain cross-linking. Elimination of fibrin γ-chain cross-linking resulted in thrombi with reduced strength that were prone to fragmentation. Analysis of embolism in vivo using Xtreme optical imaging and light sheet microscopy demonstrated that the elimination of fibrin γ-chain cross-linking resulted in increased embolization without affecting clot size or lysis. Our findings point to a central previously unrecognized role for fibrin γ-chain cross-linking in clot stability. They also indirectly indicate mechanistic targets for the prevention of thrombosis through selective modulation of fibrin α-chain but not γ-chain cross-linking by activated Factor XIII to reduce thrombus size and burden, while maintaining clot stability and preventing embolism.
Paradoxical Temporal Enlargement: An Expansion of Superficial Temporal Fat Pad Following Interfacial Technique for Pterional Craniotomy

Supplemental Digital Content is available in the text Objective: Contour irregularities in the temporal region have been reported previously after procedures involving temporal dissection. In this study, we report paradoxical temporal enlargement (PTE) following interfascial pterional craniotomy. Methods: A retrospective review of patients who underwent a unilateral transcranial procedure with frontotemporal approach at our institution between September 2013 and December 2017 was performed. Patients with a previous craniotomy or bilateral craniotomy were excluded. Radiological imaging series including computed tomography and magnetic resonance imaging were utilized to calculate temporal soft tissue volumes both preoperatively and postoperatively by using advanced software technology. Relative soft tissue volume differences between the operative side and the contralateral side were calculated at different time-points including preoperative, 3-months follow-up (3M), 12-months (12M) follow-up, and the last follow-up (LFU, over 1-year). Results: Forty-three patients were included. Mean age was 52.7 ± 4.5 years. Mean follow-up was 27.9 ± 15.8 months. Significant changes of temporal fat pad relative-volume difference were observed between the preoperative and the corresponding 3M (t [82] = −2.8865, P = 0.0050); 12M (t [77] = −4.4321, P < 0.0001), and LFU (t [74] = −4.9862, P < 0.0001) postoperative time points. No significant change of the temporalis muscle was observed between the preoperative and the corresponding 3M (P = 0.3629), 12M (P = 0.1553), or LFU (P = 0.0715). Soft tissue volume showed a significant increase on the operative side between the preoperative and the corresponding LFU (t [74] = −2.5866, P = 0.0117). Conclusions: Paradoxical temporal enlargement with more than 10% volumetric change was observed in 24% of the patients at their LFU (>1-year). This change was not due to temporalis muscle changes. Paradoxical temporal enlargement was due to hypertrophy of the superficial temporal fat pad. Before surgical correction of postoperative temporal contour changes, it is important to obtain imaging and characterize the etiology of the deformity.
Improving provision of family planning among pastoralists in Kenya: Perspectives from health care providers, community and religious leaders

ABSTRACT There exist significant inequities in access to family planning (FP) in Kenya, particularly for nomadic and semi-nomadic pastoralists. Health care providers (HCP), are key in delivering FP services. Community leaders and religious leaders are also key influencers in women’s decisions to use FP. We found limited research exploring the perspectives of both HCPs and these local leaders in this context. We conducted semi-structured interviews with HCPs (n=4) working in facilities in Wajir and Mandera, and community leaders (n=4) and religious leaders (n=4) from the nomadic and semi-nomadic populations the facilities serve. We conducted deductive and inductive thematic analysis. Three overarching themes emerged: perception of FP as a health priority, explanations for low FP use, and recommendations to improve access. Four overlapping sub-themes explained low FP use: desire for large families, tension in FP decision-making, religion and culture, and fears about FP. Providers were from different socio-demographic backgrounds to the communities they served, who faced structural marginalisation from health and other services. Programmes to improve FP access should be delivered alongside interventions targeting the immediate health concerns of pastoralist communities, incorporating structural changes. HCPs that are aware of religious and cultural reasons for non-use, play a key role in improving access.