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Rh complexes of a tridentate PPP ligand bearing 1,2-pyrrolediyl linkers have been prepared, including examples with the central P donor being either a phosphine or a phosphide. Three bimetallic Rh complexes containing the diamandoid Rh2P2core (P = phosphido) have been structurally and spectroscopically characterized. The Rh–Rh interaction in these three dimers was examined by way of structural comparisons and DFT investigations.

Multi-material Additive manufacturing (AM) has opened new opportunities for the creation of multifunctional structures that enables value-added structural product designs. Among the multi-material AM techniques, multi-nozzle fused filament fabrication which is a type of material extrusion technique is found to be the more popular choice for multi-material polymer fabrication. One major challenge of multi-material additive manufacturing of polymers is the poor mechanical strength at the interface of the dissimilar materials such as polylactic acid (PLA) and thermoplastic polyurethane (TPU) due to the lack of chemical affinity. Therefore, understanding the mechanical strength at the interface of these dissimilar materials becomes an important topic as it allows product designers to do necessary tweak to the design to compensate for the weaker link in the structural design. In this work, we investigated the tensile strength and the shear strength of different combinations of PLA and TPU and their respective nanocomposites, as well as the fatigue analysis of the bi-layer structures made of these dissimilar materials in a 3-point bending test configuration. Generally, when functional fillers or particles are added to the polymer in composites, they tend to adversely affect the interlaminar adhesion property and fatigue life of the soft-rigid bilayer structure. It was found, that the interlaminar tensile strength and the interlaminar shear strength can reduce as high as 44% and 78%, respectively, compared to the baseline samples with no fillers.

Background:Immune checkpoint inhibitor (ICI)-based therapy such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab became mainstream first-line systemic treatment in advanced hepatocellular carcinoma (HCC) patients since remarkably superior efficacy of ICI-based therapy compared to tyrosine kinase inhibitors (TKIs) was reported in two recent randomized controlled trials (RCTs) (IMbrave150, HIMALAYA). However, the optimal second-line therapy after treatment failure of first-line ICI-based therapy remains unknown as no RCT has examined this issue. Summary:Therefore, at present, most clinicians are empirically treating patients with TKIs or retrial of ICI or locoregional treatment (LRT) modality such as transarterial therapy, radiofrequency ablation, and radiation therapy in this clinical setting without solid evidence. In this review, we will discuss current optimal strategies for second-line treatment after the failure of first-line ICI-based therapy by reviewing published studies and ongoing prospective trials. Key Messages:Clinicians should consider carefully whether to treat the patients with TKI, other ICI-based therapy, or LRT in this situation by considering several factors including liver function reserve, performance status, adverse events of previous therapy, and presence of lesion that can consider LRT such as oligoprogression and vascular invasion. In the meantime, we await the results of ongoing prospective trials to elucidate the best management options.

The implementation of hospitality service technology is rapidly growing. Although there are practical, economic, and experiential benefits of these technologies, the increased adoption of service technologies such as mobile keys, and check-in kiosks can introduce friction points for the hotel guests. Technostress is stress induced by the usage of technology and this study is among the first to apply this notion to consumer behavior. Based on the transactional model of stress and coping, and social cognitive theory, this study examined the effects of technostress on hotel guests by using a mixed-method approach comprised of three sequential phases. A qualitative examination of guest experiences with hotel technology indicated Wi-Fi, hotel apps, and smart TVs to be the most prominent stress-inducing technologies. These technologies were also associated with four technostressors: techno-overload, techno-invasion, techno-complexity, and techno-uncertainty. Quantitative examination showed significant relationships between technology self-efficacy, one's locus of control, and technostress; additionally, technostress was shown to significantly impact guest satisfaction. The findings of this study extend technostress literature beyond workplace applications and into consumer behavior.

In this meta‐analysis, correlations of personality traits and career decision‐making self‐efficacy with self and environmental career exploration were estimated across 71 samples and a pairwise sample of 19,846. Traits included the Big Five personality traits, shyness, locus of control, vocational decision styles, and stress. Many measures of career exploration were based on scores of self and environmental exploration on the Career Exploration Survey. Results varied by characteristics with the largest effects for locus of control, vocational decision style: thinking‐feeling and self‐efficacy. Environmental exploration and self‐exploration were moderately correlated and demonstrated different relations with traits that were consistent with theory. Self‐exploration was related to openness to experience and unrelated to extraversion, while environmental exploration was correlated with extraversion. Both were similarly correlated with conscientiousness such that conscientious individuals were more likely to engage in career exploration.

Hintergrund: Leitlinien zum Myokardinfarkt (MI) empfehlen eine blutverdünnende Therapie zum Diagnosezeitpunkt. Während der MI mit ST-Streckenhebung (STEMI) präklinisch sicher detektiert werden kann, ist das akute Koronarsyndrom ohne ST-Streckenhebung (NSTE-ACS) eine Arbeitsdiagnose. Zielsetzung: Erfassung von präklinischem Loading mit Acetylsalicylsäure (ASS) und Heparin stratifiziert nach ACS-Entität und in Abhängigkeit von oraler Antikoagulation. Methoden: Die PRELOAD-Studie wurde als deutschlandweite Online-Umfrage durchgeführt. STEMI/NSTE-ACS-Szenarien wurden mit folgender Variation präsentiert: I) ohne Vorbehandlung, II) Vorbehandlung mit neuem oralem Antikoagulan (NOAK), Vorbehandlung mit Vitamin-K-Antagonist (VKA). Loading-Strategien wurden erhoben und umfassten: a) ASS, b) unfraktioniertes Heparin (UFH), c) ASS + UFH, d) kein Loading. Ergebnisse: In die Studie wurden 708 Notfallmediziner*innen eingeschlossen. Beim NSTE-ACS ohne Vorbehandlung entschieden sich 79 % für ein Loading (p< 0,001). ASS + UFH (71,4 %) war die häufigste Antwort. Beim STEMI entschlossen sich 100 % zum Loading, wobei 98,6 % ASS + UFH wählten. Beim NSTE-ACS mit NOAK-Vorbehandlung wählten 69,8 % Loading (p< 0,001). Eine VKA-Einnahme führte in 72,3 % der Fälle zum Loading (p< 0,001). ASS gefolgt von ASS + UFH waren die häufigsten Antworten. Beim STEMI war eine NOAK- bzw. VKA-Behandlung in 97,5 bzw. 96,8 % der Fälle mit einer Loading-Entscheidung verbunden (p< 0,001) – vermehrt wurde eine ASS-Monotherapie eingesetzt. Schlussfolgerungen: Präklinisches Loading ist die präferierte Behandlungsstrategie, obwohl beim NSTE-ACS die Leitlinien eine Antikoagulation erst zum Zeitpunkt der Diagnose empfehlen. Im Fall vorbestehender oraler Antikoagulation wird präklinisches Loading gehäuft in Form einer ASS-Monotherapie durchgeführt. Beim STEMI mit Notwendigkeit der sofortigen invasiven Strategie bedeutet dies eine potenzielle Unterversorgung.

Copy number variants (CNVs) are major contributors to genetic diversity and disease. While standardized methods, such as the genome analysis toolkit (GATK), exist for detecting short variants, technical challenges have confounded uniform large-scale CNV analyses from whole-exome sequencing (WES) data. Given the profound impact of rare and de novo coding CNVs on genome organization and human disease, we developed GATK-gCNV, a flexible algorithm to discover rare CNVs from sequencing read-depth information, complete with open-source distribution via GATK. We benchmarked GATK-gCNV in 7,962 exomes from individuals in quartet families with matched genome sequencing and microarray data, finding up to 95% recall of rare coding CNVs at a resolution of more than two exons. We used GATK-gCNV to generate a reference catalog of rare coding CNVs in WES data from 197,306 individuals in the UK Biobank, and observed strong correlations between per-gene CNV rates and measures of mutational constraint, as well as rare CNV associations with multiple traits. In summary, GATK-gCNV is a tunable approach for sensitive and specific CNV discovery in WES data, with broad applications.

Purpose: When organizations implement a new information system (IS), they often experience users' resistance behaviors. This study explored the effects of IS self-efficacy, perceived ease of use, perceived usefulness, and anxiety on resistance to IS change within the hospitality domain. It also compared these relationships before and after completing e-learning courses for a new IS. Design/methodology/approach: Survey responses were gathered from current and future hospitality employees. All hypotheses were tested via confirmatory factor analysis and structural equation modeling. Findings: The results demonstrated that (1) IS self-efficacy had significant effects on both perceived usefulness and perceived ease of use of IS; and (2) IS anxiety had a significant impact on resistance to IS change, both before and after completing the e-learning courses. The results also showed that self-efficacy had a significant effect on anxiety and, in turn, resistance to change, after completing the e-learning courses, but not prior to the training. Research limitations/implications: This study addressed the lack of theory-driven empirical research on predictors of user resistance to IS change, based on social cognitive theory, technology acceptance models, and user resistance research. Practical implications: Based on the findings, hospitality operators and vendors can focus on improving factors influencing user adoption of a new IS when they design and implement it. Operators can design better change management strategies to reduce resistance to IS change. Originality/value: Few investigations have been conducted to explain the relationships among the aforementioned factors, before and after completing e-learning for a hospitality IS.

ObjectivesTo determine circulating levels of antibodies (IgA, IgM, IgG1-4) in individuals with SCI as compared to uninjured individuals.Study DesignProspective, observational study.SettingOutpatient clinic of a Department of Physical Medicine and Rehabilitation and research institute in an academic medical center.ParticipantsIndividuals with chronic (≥ 1 year from injury) SCI and uninjured individuals.Outcome MeasuresSerum antibody titers were determined by commercial multiplex ELISA.ResultsBlood samples were collected from individuals with chronic SCI (N = 29, 83% males) and uninjured individuals (N = 25, 64% males). Among participants with SCI, the distribution of American Spinal Injury Association Impairment Scale (AIS) grades was: A (n = 15), B (n = 2), C (n = 4), D (n = 8). Neurological levels of injury were: cervical (n = 17), thoracic (n = 10), and lumbar (n = 2). IgA levels were significantly elevated in participants with SCI compared to uninjured participants (median: 1.98 vs. 1.21 mg/ml, P < 0.0001), with levels most elevated in individuals with motor complete injuries compared to uninjured participants (P < 0.0003). IgG2 antibodies were also significantly elevated in participants with SCI compared to uninjured participants (median: 5.98 vs. 4.37 mg/ml, P < 0.018).ConclusionsTo our knowledge, this study provides the first evidence of elevated IgA, the antibody type most prevalent at respiratory, genitourinary and gastrointestinal tracts, common sites of infections in individuals with SCI. IgG2 levels were also elevated in individuals with SCI. These data support further investigations of IgA and other antibody types in individuals with chronic SCI, which may be increasingly important in the context of emerging novel infectious diseases such as SARS-CoV-2.

Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR) ≤ 0.001 (185 at FDR ≤ 0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk. Meta-analysis with cohorts ascertained for developmental delay (DD) (n= 91,605) yielded 373 genes associated with ASD/DD at FDR ≤ 0.001 (664 at FDR ≤ 0.05), some of which differed in relative frequency of mutation between ASD and DD cohorts. The DD-associated genes were enriched in transcriptomes of progenitor and immature neuronal cells, whereas genes showing stronger evidence in ASD were more enriched in maturing neurons and overlapped with schizophrenia-associated genes, emphasizing that these neuropsychiatric disorders may share common pathways to risk.

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The neocortex is disproportionately expanded in human compared with mouse1,2, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth3. Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues. We demonstrate a strong correspondence between morphological, physiological and transcriptomic phenotypes of five human glutamatergic supragranular neuron types. These were enriched in but not restricted to layers, with one type varying continuously in all phenotypes across layers 2 and 3. The deep portion of layer 3 contained highly distinctive cell types, two of which express a neurofilament protein that labels long-range projection neurons in primates that are selectively depleted in Alzheimer’s disease4,5. Together, these results demonstrate the explanatory power of transcriptomic cell-type classification, provide a structural underpinning for increased complexity of cortical function in humans, and implicate discrete transcriptomic neuron types as selectively vulnerable in disease.

Research into the effects of mindfulness meditation on behavioral outcomes has received much interest in recent years, with benefits for both short-term memory and working memory identified. However, little research has considered the potential effects of brief mindfulness meditation interventions or the nature of any benefits for visual short-term memory. Here, we investigate the effect of a single, 8-minute mindfulness meditation intervention, presented via audio recording, on a short-term memory task for faces. In comparison with two control groups (listening to an audiobook or simply passing the time however they wished), our mindfulness meditation participants showed greater increases in visual short-term memory capacity from pre- to post-intervention. In addition, only mindfulness meditation resulted in significant increases in performance. In conclusion, a single, brief mindfulness meditation intervention led to improvements in visual short-term memory capacity for faces, with important implications regarding the minimum intervention necessary to produce measurable changes in short-term memory tasks.

Hematopoiesis is extrinsically controlled by cells of the bone marrow microenvironment, including skeletal lineage cells. The identification and subsequent studies of distinct subpopulations of maturing skeletal cells is currently limited because of a lack of methods to isolate these cells. We found that murine Lin–CD31–Sca-1–CD51+ cells can be divided into 4 subpopulations by using flow cytometry based on their expression of the platelet-derived growth factor receptors ⍺ and β (PDGFR⍺ and PDGFRβ). The use of different skeletal lineage reporters confirmed the skeletal origin of the 4 populations. Multiplex immunohistochemistry studies revealed that all 4 populations were localized near the growth plate and trabecular bone and were rarely found near cortical bone regions or in central bone marrow. Functional studies revealed differences in their abundance, colony-forming unit–fibroblast capacity, and potential to differentiate into mineralized osteoblasts or adipocytes in vitro. Furthermore, the 4 populations had distinct gene expression profiles and differential cell surface expression of leptin receptor (LEPR) and vascular cell adhesion molecule 1 (VCAM-1). Interestingly, we discovered that 1 of these 4 different skeletal populations showed the highest expression of genes involved in the extrinsic regulation of B lymphopoiesis. This cell population varied in abundance between distinct hematopoietically active skeletal sites, and significant differences in the proportions of B-lymphocyte precursors were also observed in these distinct skeletal sites. This cell population also supported pre-B lymphopoiesis in culture. Our method of isolating 4 distinct maturing skeletal populations will help elucidate the roles of distinct skeletal niche cells in regulating hematopoiesis and bone.

Patients with critical limb ischemia (CLI) often require lower extremity bypass surgery for limb salvage. A myocardial infarction (MI) is a major postoperative risk. Our objective is to assess the utility of preoperative stress test in determining patient outcomes.

Purpose: Access-related vascular complications in transfemoral transcatheter aortic valve implantation (TAVI) can be treated endovascularly or surgically. The aim of this study was to evaluate the short- and long-term outcomes of endovascular treatment compared with surgical repair for access-related vascular complications.Methods: This retrospective study was performed from January 1, 2018, to December 31, 2020. All transfemorally treated TAVI patients in whom a surgical or endovascular treatment for an access site complication was needed were included. The primary outcome was the need for any related vascular re-operation.Results: In total, 1219 transfemoral TAVI procedures were conducted during the study period. 19 patients suffered an access complication requiring endovascular treatment, while 54 patients required surgical repair. No differences were seen with regard to re-operations (endovascular 15.8% vs surgical 14.8%; p=0.919), wound infections (endovascular 0% vs surgical. 11.1%; p=0.129), and wound healing disorders (endovascular 15.8% vs surgical 29.6%; p=0.237). Patients undergoing endovascular treatment were discharged earlier (endovascular 11.2 vs surgical 14.9 days; p=0.028). After surgical repair, patients received significantly more blood transfusions than endovascularly treated patients (endovascular 1.00 vs surgical 3.1 red blood cell concentrate bags; p<0.001). No differences were found regarding the new onset of walking pain, rest pain, and ischemic ulcers during follow-up.Conclusion: In this retrospective cohort, endovascular treatment of access-related vascular complications of transfemoral TAVI procedures was safe and feasible. During the hospital stay, endovascularly treated patients received fewer blood transfusions and were discharged faster than surgically treated patients. No differences regarding clinical outcomes and re-intervention rates were seen during the follow-up.Clinical Impact Given the in this retrospective study demonstrated safety and feasibility of endovascular treatment for major access-related vascular complications, along with the in-hospital benefits and absence of follow-up disadvantages compared to surgical treatment, endovascular treatment should be considered in cases of major access-related vascular complications in transfemoral TAVI patients.

Patients undergoing carotid endarterectomy (CEA) often experience postoperative hemodynamic changes that require intravenous medications for hypo- and hypertension. Prior studies have found these changes to be associated with increased risks of 30-day mortality, stroke, myocardial infarction (MI), and length of stay (LOS). Our aim is to investigate preoperative risk factors associated with the need for postoperative intravenous medications for blood pressure control.

This consensus statement presents a comprehensive and evidence-based set of guidelines for the care of postoperative nausea and vomiting (PONV) in both adult and pediatric populations. The guidelines are established by an international panel of experts under the auspices of the American Society of Enhanced Recovery and Society for Ambulatory Anesthesia based on a comprehensive search and review of literature up to September 2019. The guidelines provide recommendation on identifying high-risk patients, managing baseline PONV risks, choices for prophylaxis, and rescue treatment of PONV as well as recommendations for the institutional implementation of a PONV protocol. In addition, the current guidelines focus on the evidence for newer drugs (eg, second-generation 5-hydroxytryptamine 3 [5-HT3] receptor antagonists, neurokinin 1 (NK1) receptor antagonists, and dopamine antagonists), discussion regarding the use of general multimodal PONV prophylaxis, and PONV management as part of enhanced recovery pathways. This set of guidelines have been endorsed by 23 professional societies and organizations from different disciplines (Appendix 1).What Other Guidelines Are Available on This Topic?Guidelines currently available include the 3 iterations of the consensus guideline we previously published, which was last updated 6 years ago1–3; a guideline published by American Society of Health System Pharmacists in 19994; a brief discussion on PONV management as part of a comprehensive postoperative care guidelines5; focused guidelines published by the Society of Obstetricians and Gynecologists of Canada,6the Association of Paediatric Anaesthetists of Great Britain & Ireland7and the Association of Perianesthesia Nursing8; and several guidelines published in other languages.9–12Why Was This Guideline Developed?The current guideline was developed to provide perioperative practitioners with a comprehensive and up-to-date, evidence-based guidance on the risk stratification, prevention, and treatment of PONV in both adults and children. The guideline also provides guidance on the management of PONV within enhanced recovery pathways.How Does This Guideline Differ From Existing Guidelines?The previous consensus guideline was published 6 years ago with a literature search updated to October 2011. Several guidelines, which have been published since, are either limited to a specific populations7or do not address all aspects of PONV management.13The current guideline was developed based on a systematic review of the literature published up through September 2019. This includes recent studies of newer pharmacological agents such as the second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, a dopamine antagonist, neurokinin 1 (NK1) receptor antagonists as well as several novel combination therapies. In addition, it also contains an evidence-based discussion on the management of PONV in enhanced recovery pathways. We have also discussed the implementation of a general multimodal PONV prophylaxis in all at-risk surgical patients based on the consensus of the expert panel.

Although neuropsychiatric disorders have an established genetic background, their molecular foundations remain elusive. This has prompted many investigators to search for explanatory biomarkers that can predict clinical outcomes. One approach uses machine learning to classify patients based on blood mRNA expression. However, these endeavors typically fail to achieve the high level of performance, stability, and generalizability required for clinical translation. Moreover, these classifiers can lack interpretability because not all genes have relevance to researchers. For this study, we hypothesized that annotation‐based classifiers can improve classification performance, stability, generalizability, and interpretability. To this end, we evaluated the models of four classification algorithms on six neuropsychiatric data sets using four annotation databases. Our results suggest that the Gene Ontology Biological Process database can transform gene expression into an annotation‐based feature space that is accurate and stable. We also show how annotation features can improve the interpretability of classifiers: as annotations are used to assign biological importance to genes, the biological importance of annotation‐based features are the features themselves. In evaluating the annotation features, we find that top ranked annotations tend contain top ranked genes, suggesting that the most predictive annotations are a superset of the most predictive genes. Based on this, and the fact that annotations are used routinely to assign biological importance to genetic data, we recommend transforming gene‐level expression into annotation‐level expression prior to the classification of neuropsychiatric conditions.

Autism spectrum disorder (ASD) is a markedly heterogeneous condition with a varied phenotypic presentation. Its high concordance among siblings, as well as its clear association with specific genetic disorders, both point to a strong genetic etiology. However, the molecular basis of ASD is still poorly understood, although recent studies point to the existence of sex‐specific ASD pathophysiologies and biomarkers. Despite this, little is known about how exactly sex influences the gene expression signatures of ASD probands. In an effort to identify sex‐dependent biomarkers and characterize their function, we present an analysis of a single paired‐end postmortem brain RNA‐Seq data set and a meta‐analysis of six blood‐based microarray data sets. Here, we identify several genes with sex‐dependent dysregulation, and many more with sex‐independent dysregulation. Moreover, through pathway analysis, we find that these sex‐independent biomarkers have substantially different biological roles than the sex‐dependent biomarkers, and that some of these pathways are ubiquitously dysregulated in both postmortem brain and blood. We conclude by synthesizing the discovered biomarker profiles with the extant literature, by highlighting the advantage of studying sex‐specific dysregulation directly, and by making a call for new transcriptomic data that comprise large female cohorts.

Missense variants located to the “molecular brake” in the tyrosine kinase hinge region of platelet-derived growth factor receptor-β, encoded by PFGFRB, can cause Penttinen-type (Val665Ala) and Penttinen-like (Asn666His) premature ageing syndromes, as well as infantile myofibromatosis (Asn666Lys and Pro660Thr). We have found the same de novo PDGFRBc.1997A>G p.(Asn666Ser) variants in two patients with lipodystrophy, acro-osteolysis and severely reduced vision due to corneal neovascularisation, reminiscent of a severe form of Penttinen syndrome with more pronounced connective tissue destruction. In line with this phenotype, patient skin fibroblasts were prone to apoptosis. Both in patient fibroblasts and stably transduced HeLa and HEK293 cells, autophosphorylation of PDGFRβ was observed, as well as increased phosphorylation of downstream signalling proteins such as STAT1, PLCγ1, PTPN11/SHP2-Tyr580 and AKT. Phosphorylation of MAPK3 (ERK1) and PTPN11/SHP2-Tyr542 appeared unaffected. This suggests that this missense change not only weakens tyrosine kinase autoinhibition, but also influences substrate binding, as both PTPN11 tyrosines (Tyr542 and Tyr580) usually are phosphorylated upon PDGFR activation. Imatinib was a strong inhibitor of phosphorylation of all these targets, suggesting an option for precision medicine based treatment.

Holistic ministry is now the standard across global missional practice, and one manifestation of integral mission is Entrepreneurial Church Planting (ECP). This occurs when business entrepreneurs and clergy members launch spiritually and economically integrated communities of faith. While it may be conceptually inviting for spiritual and business forces to comingle in reaching the lost, ECP activities need to be evaluated as to whether they are accomplishing the goals of the Great Commission and the Creation Commission. In-depth study is needed now to consider outcomes relative to goals. To that end, this study will examine the unique data trends that emerge in the case study of Kentucky-based Meridzo Ministries. Grassroots insights from case-study research will then be applied to Clemens Sedmak’s kinship model in order to posit three proxy indicators based upon interviewee data. This article argues that rather than measuring success of missions economically or spiritually, success should be gauged on the grounds of holistic relational transformation.

ABSTRACTIntroduction: Esophageal cancer is a heterogeneous cancer comprised of differing cells of origin, molecular changes, and immune microenvironments. To date, most advances have been made in chemotherapy regimens where a one-size-fits-all approach is used. As a result, there remains a lack of tailored treatment options for such a heterogeneous cancer. This paper highlights the current standard of care treatment options as well as active areas of clinical research.Areas covered: The authors review the key trials that have led to current standard of care treatment including pivotal chemotherapy and targeted therapy trials. The authors then discuss the current approved uses and future directions for immunotherapy.Expert opinion: Current treatment options lack tailored treatment strategies based on the tumor’s biology. To date, approved targeted approaches only include HER2-directed and anti-VEGFR2 therapies. Furthermore, while immunotherapy treatment response is often durable, few clear predictive biomarkers for response have been identified. Future research should focus on characterizing additional molecular targets for therapeutic intervention and predictive biomarkers for immunotherapy, as well as combination approaches of immunotherapy with other therapeutic modalities to increase response rate. Ultimately, the field should strive to develop personalized treatment options based on a tumor’s molecular profile, microenvironment, and neo-antigen expression.

The pangenotypic direct-acting antiviral regimen of glecaprevir coformulated with pibrentasvir is approved to treat chronic hepatitis C virus (HCV) genotype 1–6 infection in adults. In registrational studies, 84 (99%) of 85 patients with HCV genotype 5 or 6 infection achieved a sustained virological response (SVR) with glecaprevir/pibrentasvir, with no virological failures. To increase the body of data for these less prevalent genotypes, ENDURANCE-5,6 evaluated the efficacy and safety of glecaprevir/pibrentasvir exclusively in patients infected with HCV genotype 5 or 6.

As more print media move to online, news and media websites have evolved with increasing complexity in content, design, and monetization strategies. In this article, the authors examined and reported the web design patterns of 150 leading news and media websites in six different categories: TV news, online newspapers, online magazines, and technology news, sports news, and business news, using 28 analytics metrics in four dimensions: content structure, multimedia, social sharing, and advertising placements.

Currently, the demand for more reliable drug screening devices has made scientists and researchers develop novel potential approaches to offer an alternative to animal studies. Organ‐on‐chips are newly emerged platforms for drug screening and disease metabolism investigation. These microfluidic devices attempt to recapitulate the physiological and biological properties of different organs and tissues using human‐derived cells. Recently, the synergistic combination of additive manufacturing and microfluidics has shown a promising impact on improving a wide array of biological models. In this review, different methods are classified using bioprinting to achieve the relevant biomimetic models in organ‐on‐chips, boosting the efficiency of these devices to produce more reliable data for drug investigations. In addition to the tissue models, the influence of additive manufacturing on microfluidic chip fabrication is discussed, and their biomedical applications are reviewed. Demands for reliable drug screening and alternatives to animal studies, organ‐on‐a‐chips, are attracting researchers’ attention as one of the most promising biomedical tools for this mean. This manuscript contains a summary of different bioprinting techniques to facilitate the construction of more complex and relevant biological models, enhancing automation and reproducibility and making the process high throughput.

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