bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Checkpoint Inhibitors in Organ Transplant Patients
Authors: Kittai Adam S. , Oldham Hayden , Cetnar Jeremy , Taylor Matthew
Published: July 2017

Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant. Excluding these patients was deliberate due to concern that immune checkpoint inhibitor therapy could lead to graft rejection. The PD-1 and CTLA-4 pathways are essential to downregulate our immune system in the setting of T-cell activation to prevent autoimmunity. Furthermore, both pathways are implicated in transplanted organ tolerance and modulation of the pathways may inadvertently lead to peripheral transplant rejection. Currently, there are no guidelines for the treatment of patients with immune checkpoint inhibitors in the setting of a prior organ transplant. Thus far, there are only 10 reported cases of patients in the literature who were treated in this setting. Two additional cases are reported herein, including 1 patient with a prior cardiac transplant receiving nivolumab for non–small cell lung cancer. Of the 12 cases, 4 patients experienced organ rejection. From these observations, the authors hypothesize factors that affect safety and of this treatment modality in this patient population. These factors include the integral role of the PD-1 pathway compared with the CTLA-4 pathway in organ acceptance, sequential implementation of different immune checkpoint inhibitor classes, length of time with a transplant before therapy, strength of immunosuppressive agents to prevent organ transplant rejection, and immunogenicity of the particular organ grafted. Although limited cases have been reported, there are circumstances in which immune checkpoint inhibitors have been used in the setting of organ transplantation without resulting in organ rejection. A thorough discussion with the patient of the potential risks, including graft rejection, and benefits of this therapy is necessary before beginning this treatment. More research is needed to explore the safety and efficacy of immune checkpoint inhibitors in the setting of organ transplantation.
Cutaneous Indeterminate Cell Histiocytosis of Donor Origin After Allogeneic Hematopoietic Stem-Cell Transplantation
Authors: Santos-Briz Angel , Román Concepción , Corral Rocío , de Dios Alvaro , Vázquez Lourdes , Ludeña María D.
Published: July 2017

Allogeneic hematopoietic stem-cell transplantation and solid-organ transplantation are associated with an increased risk of secondary neoplasms. Indeterminate cell histiocytosis (ICH) is a rare disease composed of so-called indeterminate cells, an alleged cutaneous dendritic cell subset displaying histological and some ultrastructural and immunophenotypic features of Langerhans cells but lacking Birbeck granules. We report a case of cutaneous ICH occurring after allogeneic hematopoietic stem-cell transplantation for a myelodysplastic syndrome in a 56-year-old man. Microsatellite analysis demonstrated that the neoplastic cells were derived from the donor's hematopoietic system. This case broadens the spectrum of complications after stem-cell transplantation and demonstrates that cutaneous ICH in the setting of myelodysplastic syndromes may have a nonrelated origin to dysplastic myeloid cells.
Leukocytoclastic Vasculitis and Dermal Perivascular Hemophagocytosis Associated With Adalimumab Therapy for Rheumatoid Arthritis
Authors: Muto Jun , Usami Jun , Watanabe Daisuke
Published: July 2017

Tumor necrosis factor (TNF)-α inhibitors target TNF-α to effectively treat autoimmune inflammatory conditions, such as rheumatoid arthritis. However, many cases of cutaneous and systemic vasculitis related to TNF-α inhibitors have been reported in the literature. Here, the authors report the first case of a 61-year-old Japanese woman who developed leukocytoclastic vasculitis with cutaneous perivascular hemophagocytosis, which was related to elevated cytokines and immune complexes after initiating adalimumab for rheumatoid arthritis without evidence of hemophagocytic syndrome and rarely encountered in the skin. The patient was successfully treated by discontinuing adalimumab and initiating corticosteroid therapy, which should be considered as the treatment of choice. We believe that our case confirms and adds to the evidence pertaining to the involvement of TNF-α in dermal perivascular hemophagocytosis, a histologic finding rarely observed in the skin.
Lifelong estradiol exposure and risk of depressive symptoms during the transition to menopause and postmenopause
Authors: Marsh Wendy K. , Bromberger Joyce T. , Crawford Sybil L. , Leung Katherine , Kravitz Howard M. , Randolph John F. , Joffe Hadine , Soares Claudio N.
Published: July 2017

Objective:

Depression risk increases during the menopausal transition (MT) and initial postmenopausal years—both times of significant fluctuations of estrogen. Research to date provides limited support for the hypothesis that estrogen fluctuations play a role in the greater susceptibility to midlife depression. Importantly, not all women report depressive symptoms during the MT, and recent reports suggest that duration of exposure to estradiol throughout the adult years may also play a role in vulnerability to depression. This study examines patterns of estrogen exposure during the reproductive years and risk of depression during the MT and early postmenopausal years.

Methods:

A longitudinal, US community-based, multiethnic study of menopause. Data were collected at baseline and annually for 10 years, and included 1,306 regularly menstruating premenopausal women, aged 42 to 52 years at study entry. The main outcome was incidence of high level of depressive symptoms, Center for Epidemiological Studies Depression Scale (CES-D) score at least 16, in the MT and initial postmenopausal years, independent of premenopausal depression symptoms. Risk factors examined were duration of estrogen exposure (menarche to MT), duration of hormonal birth control use, pregnancies, and lactation.

Results:

In a multivariate adjusted model, longer duration of estrogen exposure from menarche to MT onset was significantly associated with a reduced risk of depression (CES-D ≥16) during the MT and 10 years or less postmenopause (odds ratio 0.85, 95% confidence interval 0.78-0.92). Longer duration of birth control use was associated with a decreased risk of CES-D at least 16 (odds ratio 0.90, 95% confidence interval 0.83-0.98), but number of pregnancies or breastfeeding was not.

Conclusions:

Patterns of reproductive lifetime exposure to estrogen are associated with risk of high depressive symptoms during the MT and initial postmenopausal years; longer exposure to estrogen seemed protective.
Preclinical Models of Ovarian Cancer: Pathogenesis, Problems, and Implications for Prevention
Authors: KARNEZIS ANTHONY N. , CHO KATHLEEN R.
Published: July 2017

Preclinical models are relatively underutilized and underfunded resources for modeling the pathogenesis and prevention of ovarian cancers. Several reviews have detailed the numerous published models of ovarian cancer. In this review, we will provide an overview of experimental model systems, their strengths and limitations, and use selected models to illustrate how they can be used to address specific issues about ovarian cancer pathogenesis. We will then highlight some of the preclinical prevention studies performed to date and discuss experiments needed to address important unanswered questions about ovarian cancer prevention strategies.
The Ophthalmology Surgical Competency Assessment Rubric for Trabeculectomy
Authors: Green Catherine M. , Salim Sarwat , Edward Deepak P. , Mudumbai Raghu C. , Golnik Karl
Published: July 2017

Purpose:

To produce an internationally valid tool to assess skill in performing trabeculectomy surgery.

Methods:

A panel of 5 experts developed a tool for assessing trabeculectomy surgery by using a modified Dreyfus scale of skill acquisition and providing descriptors for each level of skill for each category. The tool was then reviewed by a panel of 10 international content experts for their constructive comments, which were incorporated into the final rubric tool.

Results:

A final rubric, incorporating the suggestions of the international panel, published here as the ICO-OSCAR: Trabeculectomy.

Conclusions:

The tool ICO-OSCAR: Trabeculectomy has content and face validity. It can be used internationally to assess trabeculectomy surgery skill. Predictive and construct validity, and reliability are yet to be determined.
A Randomized Controlled Study of a Fully Liquid DTaP-IPV-HB-PRP-T Hexavalent Vaccine for Primary and Booster Vaccinations of Healthy Infants and Toddlers in Latin America
Authors: López Pío , Arguedas Mohs Adriano , Abdelnour Vásquez Arturo , Consuelo-Miranda Maria , Feroldi Emmanuel , Noriega Fernando , Jordanov Emilia , B′Chir Siham , Zambrano Betzana
Published: July 2017

Background:

Hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-HB-PRP-T)–containing vaccines are increasingly the standard of care. This study evaluated the primary series (NCT01177722) and booster (NCT01444781) of a fully liquid DTaP-IPV-HB-PRP-T vaccine in Latin America.

Methods:

Infants (N = 1375) received hepatitis B vaccine at birth and were randomized to one of 3 batches of the investigational DTaP-IPV-HB-PRP-T or licensed control vaccine (DTaP-HB-IPV//PRP-T) at 2–4 to 6 months of age, coadministered with 7-valent pneumococcal conjugate vaccine (PCV7) (2-4-6 months) and rotavirus vaccine (2–4 months). A booster of either DTaP-IPV-HB-PRP-T or control was given at 12–24 months, coadministered with PCV7. Immunogenicity was assessed by validated assays and safety from parental reports.

Results:

Primary series seroprotection and vaccine response rates were equivalent for DTaP-IPV-HB-PRP-T batches. For pooled batches, noninferiority to the control vaccine was demonstrated for each antigen. There were no descriptive differences in antibody persistence or booster response between DTaP-IPV-HB-PRP-T and the control. The booster responses to either vaccine following DTaP-IPV-HB-PRP-T primary series or to DTaP-IPV-HB-PRP-T following a control vaccine primary series were similar. The anti-aP component (filamentous hemagglutinin [FHA] and pertussis toxin [PT]) vaccine response and anti-Haemophilus influenzae type b (PRP) series seroprotection (≥0.15 µg/mL) rates were ≥73.0% after 2 primary series doses. Antipyretics had no effect on the immune response, and an extra (oral) polio vaccination had no effect on the antipolio booster response. Responses to PCV7 and rotavirus vaccine were similar for each coadministration. There were no safety concerns observed with any vaccine.

Conclusions:

These results confirm the suitability of the fully liquid DTaP-IPV-HB-PRP-T vaccine for primary and booster vaccination of infants.
A Modified Supine Position Facilitates Bladder Function in Patients Undergoing Percutaneous Coronary Intervention
Authors: Liu Yisi , Zhang Ying , Wu Ying , Elliott Malcolm
Published: July 2017

Background:

Percutaneous coronary intervention (PCI) is currently the most common intervention for cardiovascular disease. Standard care after PCI typically involves a period of bed rest in the supine position, but this position creates voiding difficulties.

Objective:

This study aimed to determine whether a modified supine position could facilitate bladder emptying after PCI.

Method:

A randomized controlled trial involving 300 patients was conducted. Patients in the intervention group were nursed in the supine position with the bed tilted 20° upright and with a pillow between their feet and the end of the bed. Patients in the control group received standard care, which was supine positioning.

Results:

One hundred fifty patients were allocated to the intervention group (100 men, 50 women), and 150 were allocated to the control group (103 men, 47 women). Baseline data did not differ between the 2 groups. Patients in the intervention group had significantly better bladder function as evidenced by a shorter time to the first void (5 vs 15 minutes) and fewer patients requiring voiding assistance (8.6% vs 35.3%). Residual urinary volumes were also much lower in the intervention group (88.71 vs 248.22 mL, P < .001).

Conclusions:

This study demonstrates that a modified supine position can reduce the incidence of impaired micturition and the preservation of normal bladder function after PCI.
Fourteen Day In Vivo Testing of a Compliant Thoracic Artificial Lung
Authors: Skoog David J. , Pohlmann Joshua R. , Demos David S. , Scipione Christopher N. , Iyengar Amit , Schewe Rebecca E. , Suhaib Ahmed B. , Koch Kelly L. , Cook Keith E.
Published: July 2017

The compliant thoracic artificial lung (cTAL) has been studied in acute in vivo and in vitro experiments. The cTAL’s long-term function and potential use as a bridge to lung transplantation are assessed presently. The cTAL without anticoagulant coatings was attached to sheep (n = 5) via the pulmonary artery and left atrium for 14 days. Systemic heparin anticoagulation was used. Compliant thoracic artificial lung resistance, cTAL gas exchange, hematologic parameters, and organ function were recorded. Two sheep were euthanized for nondevice-related issues. The cTAL’s resistance averaged 1.04 ± 0.05 mmHg/(L/min) with no statistically significant increases. The cTAL transferred 180 ± 8 ml/min of oxygen with 3.18 ± 0.05 L/min of blood flow. Except for transient surgical effects, organ function markers were largely unchanged. Necropsies revealed pulmonary edema and atelectasis but no other derangements. Hemoglobin levels dropped with device attachment but remained steady at 9.0 ± 0.1 g/dl thereafter. In a 14 day experiment, the cTAL without anticoagulant coatings exhibited minimal clot formation. Sheep physiology was largely unchanged except for device attachment-related hemodilution. This suggests that patients treated with the cTAL should not require multiple blood transfusions. Once tested with anticoagulant coatings and plasma resistant gas exchange fiber, the cTAL could serve as a bridge to transplantation.
The Clinical and Economic Effects of Targeted Bowel Preparation
Authors: Kurlander Jacob E. , Sultan Shahnaz , Saini Sameer D.
Published: July 2017

Background:

Colonoscopy bowel preparation failure is common, costly, and clinically harmful. Prediction models can identify patients at high risk for preparation failure, but they are rarely used.

Goals:

To investigate the clinical and economic effects of using a more intensive preparation upfront (a “targeted” strategy) for patients identified as high risk for preparation failure.

Study:

We developed a Markov decision analytic model to compare usual care with a targeted strategy. Usual care consisted of a 4 L preparation, followed by a 2-day preparation in the event of preparation failure. The targeted strategy consisted of a 4 L preparation for low-risk patients, and upfront 2 days preparation for high-risk patients. Base-case values were gathered from literature review. Under each strategy, we calculated days spent preparing for, or undergoing, colonoscopy (patient burden), and cost per patient (payer perspective). Sensitivity analyses were performed.

Results:

In the base case, the targeted strategy resulted in a similar patient burden compared with usual care (2.56 vs. 2.51 d, respectively). However, it substantially reduced cost per patient ($1254 vs. $1343) by reducing the number of colonoscopies. In sensitivity analyses, the targeted strategy reduced cost across the entire plausible range of risk of preparation failure and prediction model sensitivity and specificity. The targeted strategy resulted in less patient burden than usual care when (1) preparation failure risk exceeded 20%; (2) prediction sensitivity exceeded 73%; or (3) prediction specificity exceeded 76%.

Conclusions:

Targeted bowel preparation is likely to reduce costs associated with repeat colonoscopy with minimal effect on patient burden.
Higher Thioguanine Nucleotide Metabolite Levels are Associated With Better Long-term Outcomes in Patients With Inflammatory Bowel Diseases
Authors: Yarur Andres J. , Gondal Bilal , Hirsch Ayal , Christensen Britt , Cohen Russell D. , Rubin David T.
Published: July 2017

Goals:

The aim of this study was to assess whether sustained 6-thioguaninenucleotide (6-TGN) levels were associated with improved long-term outcomes in patients with inflammatory bowel diseases (IBD).

Background:

Cross-sectional data have shown that thiopurine metabolites are correlated with clinical efficacy in patient receiving thiopurines for IBD but the role for serial measurements through treatment course is unclear.

Study:

We conducted a retrospective cohort study including patients with IBD on thiopurine monotherapy and had serial 6-TGN levels measured. Predictive variables included demographics, disease phenotype, 6-TGN levels (nadir, median, and peak levels). The primary outcome was the development of a disease relapse. The secondary outcome was the need for IBD surgery.

Results:

Two hundred eighteen 6-TGN samples from 87 patients were analyzed. Nadir and median 6-TGN levels were significantly higher in patients who did not relapse [185 and 233 pmol per 8×108 red blood cells (RBCs)] as compared with levels in patients who did relapse (150 and 167 pmol per 8×108 RBCs, P=0.025) but there was no significant difference in peak 6-TGN level. When adjusted for confounding factors, a nadir 6-TGN level ≥161 and a median 6-TGN level ≥264 were associated with a significant decrease in the rate of disease exacerbation (hazard ratio: 0.5; 95% confidence interval, 0.26-0.87; P=0.016 and hazard ratio: 0.4; 95% confidence interval, 0.2-0.82; P=0.14).

Conclusions:

Serial thiopurine metabolite level assessments and dose adjustment aiming to maintain higher 6-TGN levels may be helpful to improve long-term outcomes in patients with IBD.
Three-dimensional head-mounted gaming task procedure maximizes effects of vestibular rehabilitation in unilateral vestibular hypofunction: a randomized controlled pilot trial
Authors: Micarelli Alessandro , Viziano Andrea , Augimeri Ivan , Micarelli Domenico , Alessandrini Marco
Published: July 2017

Considering the emerging advantages related to virtual reality implementation in clinical rehabilitation, the aim of the present study was to discover possible (i) improvements achievable in unilateral vestibular hypofunction patients using a self-assessed head-mounted device (HMD)-based gaming procedure when combined with a classical vestibular rehabilitation protocol (HMD group) as compared with a group undergoing only vestibular rehabilitation and (ii) HMD procedure-related side effects. Therefore, 24 vestibular rehabilitation and 23-matched HMD unilateral vestibular hypofunction individuals simultaneously underwent a 4-week rehabilitation protocol. Both otoneurological measures (vestibulo-ocular reflex gain and postural arrangement by studying both posturography parameters and spectral values of body oscillation) and performance and self-report measures (Italian Dizziness Handicap Inventory; Activities-specific Balance Confidence scale; Zung Instrument for Anxiety Disorders, Dynamic Gait Index; and Simulator Sickness Questionnaire) were analyzed by means of a between-group/within-subject analysis of variance model. A significant post-treatment between-effect was found, and the HMD group demonstrated an overall improvement in vestibulo-ocular reflex gain on the lesional side, in posturography parameters, in low-frequency spectral domain, as well as in Italian Dizziness Handicap Inventory and Activities-specific Balance Confidence scale scores. Meanwhile, Simulator Sickness Questionnaire scores demonstrated a significant reduction in symptoms related to experimental home-based gaming tasks during the HMD procedure. Our findings revealed the possible advantages of HMD implementation in vestibular rehabilitation, suggesting it as an innovative, self-assessed, low-cost, and compliant tool useful in maximizing vestibular rehabilitation outcomes.
Nuclear CRX and FOXJ1 Expression Differentiates Non–Germ Cell Pineal Region Tumors and Supports the Ependymal Differentiation of Papillary Tumor of the Pineal Region
Authors: Coy Shannon , Dubuc Adrian M. , Dahiya Sonika , Ligon Keith L. , Vasiljevic Alexandre , Santagata Sandro
Published: July 2017

Papillary tumor of the pineal region (PTPR) is a neuroepithelial neoplasm first described in 2003. Despite the anatomic association of PTPR with the pineal gland, the features of these tumors resemble those of the ependymal circumventricular subcommissural organ (SCO) of the posterior third ventricle. Given the presumed distinct derivation of PTPR and pineal parenchymal tumors, we hypothesized that expression of lineage-specific transcription factors could distinguish these tumors and provide additional insight into the differentiation of PTPR. A broad series of pineal region samples was reviewed, including 7 benign pineal glands, 4 pineal cysts, 13 pineocytomas, 28 pineal parenchymal tumors of intermediate differentiation, 11 pineoblastomas, and 18 PTPR. All samples were evaluated by immunohistochemistry for expression of CRX, a master transcriptional regulator of photoreceptor differentiation expressed in pineal gland and retina and/or FOXJ1, a master transcriptional regulator of ciliogenesis expressed in normal ependymal cells and ependymal neoplasms. Diffuse nuclear CRX expression is present in 100% of pineal samples. FOXJ1 is negative in all pineal samples. CRX staining is present in 53% of PTPR, though expression is nearly always limited to rare cells. Diffuse nuclear FOXJ1 expression is present in 100% of PTPR. Fetal human SCO diffusely expressed FOXJ1 but was negative for CRX. Immunohistochemistry for FOXJ1 and CRX differentiates non–germ cell pineal region tumors with high sensitivity and specificity, including pineal parenchymal tumors and PTPR. Our findings support the hypothesis that PTPR have ependymal differentiation and are phenotypically more similar to SCO than pineal gland.
Dedifferentiated Liposarcoma With Epithelioid/Epithelial Features
Authors: Makise Naohiro , Yoshida Akihiko , Komiyama Motokiyo , Nakatani Fumihiko , Yonemori Kan , Kawai Akira , Fukayama Masashi , Hiraoka Nobuyoshi
Published: July 2017

Dedifferentiated liposarcoma (DDLPS) demonstrates a variety of growth patterns, and their histologic resemblance to other spindle cell mesenchymal tumors has been widely recognized. However, epithelioid morphology in DDLPS has only rarely been documented. Here, we report 6 cases of DDLPS with striking epithelioid/epithelial features. The patients were 5 men and 1 woman with a median age of 61 years. All tumors were located in the internal trunk. During follow-up of 1 to 41 months, local recurrence, distant metastases, and tumor-related death occurred in 4, 2, and 4 patients, respectively. Beside well-differentiated liposarcoma component and conventional high-grade spindle cell morphology, all tumors focally exhibited growth comprising small or large epithelioid cells in diffuse or sheet-like proliferation. Rhabdoid cells were present in 2 cases. All 5 tumors tested harbored MDM2 amplification. Cytokeratin and/or epithelial membrane antigen were at least focally positive in all 5 tumors tested. One case contained a small focus of novel heterologous epithelial differentiation with acinar structures, wherein cytokeratin, MOC31, and claudin-4 were diffusely expressed and H3K27me3 expression was lost. DDLPS with epithelioid/epithelial features may lead to misdiagnosis of carcinoma or mesothelioma, and their diagnosis should be based on correlation with clinicopathologic and molecular findings. The epithelioid morphology in DDLPS may suggest an aggressive behavior based on this small series. In addition, we document 2 cases of MDM2-amplified undifferentiated neoplasm with epithelioid features in the internal trunk that lacked association with well-differentiated liposarcoma histology and showed rapid clinical course. Whether these latter tumors belong to DDLPS with epithelioid features requires further study.
Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions
Authors: Hechtman Jaclyn F. , Benayed Ryma , Hyman David M. , Drilon Alexander , Zehir Ahmet , Frosina Denise , Arcila Maria E. , Dogan Snjezana , Klimstra David S. , Ladanyi Marc , Jungbluth Achim A.
Published: July 2017

Activating neurotrophic tyrosine receptor kinase (NTRK) fusions, typically detected using nucleic-acid based assays, are highly targetable and define certain tumors. Here, we explore the utility of pan-TRK immunohistochemistry (IHC) to detect NTRK fusions. NTRK rearrangements were detected prospectively using MSK-IMPACT, a DNA-based next-generation sequencing assay. Transcription of novel NTRK rearrangements into potentially functional fusion transcripts was assessed via Archer Dx fusion assay. Pan-Trk IHC testing with mAb EPR17341 was performed on all NTRK rearranged cases and 20 cases negative for NTRK fusions on Archer. Of 23 cases with NTRK rearrangements, 15 had known activating fusions. Archer detected fusion transcripts in 6 of 8 novel NTRK rearrangements of uncertain functional significance. Pan-Trk IHC was positive in 20 of 21 cases with NTRK fusion transcripts confirmed by Archer. The discordant negative case was a mismatch repair- deficient colorectal carcinoma with an ETV6-NTRK3 fusion. All 20 additional Archer-negative cases had concordant pan-TRK IHC results. Pan-Trk IHC sensitivity and specificity for transcribed NTRK fusions was 95.2% and 100%, respectively. All positive IHC cases had cytoplasmic staining while the following fusion partner-specific patterns were discovered: all 5 LMNA-NTRK1 fusions displayed nuclear membrane accentuation, all 4 TPM3/4 fusions displayed cellular membrane accentuation, and half (3/6) of ETV6-NTRK3 fusions displayed nuclear staining. Pan-Trk IHC is a time-efficient and tissue-efficient screen for NTRK fusions, particularly in driver-negative advanced malignancies and potential cases of secretory carcinoma and congenital fibrosarcoma. Pan-Trk IHC can help determine whether translation occurs for novel NTRK rearrangements.
ETV6 Gene Rearrangements Characterize a Morphologically Distinct Subset of Sinonasal Low-grade Non–intestinal-type Adenocarcinoma
Authors: Andreasen Simon , Skálová Alena , Agaimy Abbas , Bishop Justin A. , Laco Jan , Leivo Ilmo , Franchi Alessandro , Larsen Stine R. , Erentaite Daiva , Ulhøi Benedicte P. , von Buchwald Christian , Melchior Linea C. , Michal Michal , Kiss Katalin
Published: July 2017

Low-grade sinonasal adenocarcinomas (low-grade SNACs) of the sinonasal tract comprise a poorly characterized and histologically heterogeneous group of tumors. We describe three cases of a histologically distinct variant of low-grade SNAC characterized by ETV6 gene rearrangements. The patients included 2 women (aged 32 and 88 y) and a man (aged 75 y); all were initially treated with surgery alone. Follow-up ranged from 9 to 170 months with one patient having 2 local recurrences and none experiencing distant or regional metastases. Tumors were composed of cytologically bland columnar and cuboidal eosinophilic tumor cells with basally located nuclei arranged in tubular and tubulotrabecular patterns. Immunohistochemically, CK7, DOG1, GCDFP-15, and SOX10 were positive in all cases, and vimentin was positive in 2 cases. Scattered single cells or small groups of tumor cells were S-100 positive. Only one case had weak, focal expression of GATA3, and mammaglobin was consistently negative. Two cases had ETV6-NTRK3 gene fusions, whereas ETV6 had an unknown fusion partner gene in one case. The highly similar morphology, immunohistochemical profile, and genetics of the presented cases are suggestive of a specific disease. Although translocation-associated adenocarcinomas in the sinonasal tract have previously been described exclusively as salivary-type carcinomas, we present the first type of carcinoma characterized by recurrent genetic rearrangements and distinct phenotype occurring exclusively in the sinonasal tract with no known major salivary gland counterpart. We provisionally designate this tumor ETV6-rearranged low-grade SNAC. Identification of additional cases is necessary to fully appreciate the morphologic and biological spectrum of this disease.
Predictors of Outcome in Adenoid Cystic Carcinoma of Salivary Glands
Authors: Xu Bin , Drill Esther , Ho Allen , Ho Alan , Dunn Lara , Prieto-Granada Carlos Nicolas , Chan Timothy , Ganly Ian , Ghossein Ronald , Katabi Nora
Published: July 2017

Adenoid cystic carcinoma (ACC) is the second most common salivary gland malignancy and it has a high rate of recurrences and a poor long-term prognosis. Our aim was to assess the prognostic factors in ACC and study MYB
-NFIB fusion and MYB protein expression in a large retrospective cohort of 135 patients with a median follow-up of 6.3 years. The 5- and 10-year local recurrence-free survival (RFS) rate of 94% and 78%, 5- and 10-year distant metastasis survival rate of 77% and 58%, and 5- and 10-year RFS of 66% and 44%. The following features were identified as adverse prognostic factors of RFS on univariate analysis: large tumor size, solid growth pattern, increased mitoses, positive margin, American Joint Committee on Cancer clinical staging, high-grade transformation, vascular invasion, nuclear atypia, open chromatin, prominent nucleoli, and tumor necrosis. However, on multivariate analysis, only increased mitoses (≥5/10 high-power fields), any solid growth pattern, and advanced American Joint Committee on Cancer TNM staging were independent adverse predictors for RFS. MYB immunoexpression and MYB-NFIB translocation were common findings in ACC, occurring in 72% and 59% of the tested ACCs, respectively. The sensitivity and specificity of MYB immunohistochemistry in detecting MYB-NFIB fusion was relatively low at 78% sensitivity and 50% specificity. The high prevalence of alterations leading to high expression of the MYB transcription factor family suggests that targeted approaches developed to suppress the expression of these oncogenic transcription factors and/or the transcriptional activity of these proteins would be a rational therapeutic approach to investigate in ACC.
Toward a Biopsychosocial Ecology of the Human Microbiome, Brain-Gut Axis, and Health
Authors: Maier Karl J. , al'Absi Mustafa
Published: July 2017

Objective

Rapidly expanding insights into the human microbiome and health suggest that Western medicine is poised for significant evolution, or perhaps revolution—this while medicine continues on a trajectory from reductionism to a biopsychosocial (BPS) paradigm recognizing biological, psychological, and social influences on health. The apparent sensitivity of the microbiota to perturbations across BPS domains suggests that a broad and inclusive framework is needed to develop applicable knowledge in this emerging area. We outline an ecological framework of the human microbiome by extending the BPS concept to better incorporate environmental and human factors as members of a global, dynamic set of systems that interact over time.

Methods

We conducted a selective literature review across disciplines to integrate microbiome research into a BPS framework.

Results

The microbiome can be understood in terms of ecological systems encompassing BPS domains at four levels: (a) immediate (molecular, genetic, and neural processes), (b) proximal (physiology, emotion, social integration), (c) intermediate (built environments, behaviors, societal practices), and (d) distal (physical environments, attitudes, and broad cultural, economic, and political factors). The microbiota and host are thus understood in terms of their immediate interactions and the more distal physical and social arenas in which they participate.

Conclusions

A BPS ecological paradigm encourages replicable, generalizable, and interdisciplinary/transdisciplinary research and practices that take into account the vast influences on the human microbiome that may otherwise be overlooked or understood out of context. It also underscores the importance of sustainable bioenvironmental, psychological, and social systems that broadly support microbial, neural, and general health.
The evolution of diatoms and their biogeochemical functions
Authors: Benoiston Anne-Sophie , Ibarbalz Federico M. , Bittner Lucie , Guidi Lionel , Jahn Oliver , Dutkiewicz Stephanie , Bowler Chris
Published: July 2017

In contemporary oceans diatoms are an important group of eukaryotic phytoplankton that typically dominate in upwelling regions and at high latitudes. They also make significant contributions to sporadic blooms that often occur in springtime. Recent surveys have revealed global information about their abundance and diversity, as well as their contributions to biogeochemical cycles, both as primary producers of organic material and as conduits facilitating the export of carbon and silicon to the ocean interior. Sequencing of diatom genomes is revealing the evolutionary underpinnings of their ecological success by examination of their gene repertoires and the mechanisms they use to adapt to environmental changes. The rise of the diatoms over the last hundred million years is similarly being explored through analysis of microfossils and biomarkers that can be traced through geological time, as well as their contributions to seafloor sediments and fossil fuel reserves. The current review aims to synthesize current information about the evolution and biogeochemical functions of diatoms as they rose to prominence in the global ocean.

This article is part of the themed issue ‘The peculiar carbon metabolism in diatoms'.
Inorganic carbon availability in benthic diatom communities: photosynthesis and migration
Authors: Marques da Silva Jorge , Cruz Sónia , Cartaxana Paulo
Published: July 2017

Diatom-dominated microphytobenthos (MPB) is the main primary producer of many intertidal and shallow subtidal environments, being therefore of critical importance to estuarine and coastal food webs. Owing to tidal cycles, intertidal MPB diatoms are subjected to environmental conditions far more variable than the ones experienced by pelagic diatoms (e.g. light, temperature, salinity, desiccation and nutrient availability). Nevertheless, benthic diatoms evolved adaptation mechanisms to these harsh conditions, including the capacity to move within steep physical and chemical gradients, allowing them to perform photosynthesis efficiently. In this contribution, we will review present knowledge on the effects of dissolved inorganic carbon (DIC) availability on photosynthesis and productivity of diatom-dominated MPB. We present evidence of carbon limitation of photosynthesis in benthic diatom mats and highly productive MPB natural communities. Furthermore, we hypothesize that active vertical migration of epipelic motile diatoms could overcome local depletion of DIC in the photic layer, providing the cells alternately with light and inorganic carbon supply. The few available longer-term experiments on the effects of inorganic carbon enrichment on the productivity of diatom-dominated MPB have yielded inconsistent results. Therefore, further studies are needed to properly assess the response of MPB communities to increased CO
2
and ocean acidification related to climate change.

This article is part of the themed issue ‘The peculiar carbon metabolism in diatoms’.
Acquisition and metabolism of carbon in the Ochrophyta other than diatoms
Authors: Raven John A. , Giordano Mario
Published: July 2017

The acquisition and assimilation of inorganic C have been investigated in several of the 15 clades of the Ochrophyta other than diatoms, with biochemical, physiological and genomic data indicating significant mechanistic variation. Form ID Rubiscos in the Ochrophyta are characterized by a broad range of kinetics values. In spite of relatively high K0.5CO2and low CO2: O2selectivity, diffusive entry of CO2occurs in the Chrysophyceae and Synurophyceae. Eustigmatophyceae and Phaeophyceae, on the contrary, have CO2concentrating mechanisms, usually involving the direct or indirect use of. This variability is possibly due to the ecological contexts of the organism. In brown algae, C fixation generally takes place through a classical C3 metabolism, but there are some hints of the occurrence of C4 metabolism and low amplitude CAM in a few members of the Fucales. Genomic data show the presence of a number of potential C4 and CAM genes in Ochrophyta other than diatoms, but the other core functions of many of these genes give a very limited diagnostic value to their presence and are insufficient to conclude that C4 photosynthesis is present in these algae.

This article is part of the themed issue ‘The peculiar carbon metabolism in diatoms'.
Mechanisms of carbon dioxide acquisition and CO
2
sensing in marine diatoms: a gateway to carbon metabolism
Authors: Matsuda Yusuke , Hopkinson Brian M. , Nakajima Kensuke , Dupont Christopher L. , Tsuji Yoshinori
Published: July 2017

Diatoms are one of the most successful marine eukaryotic algal groups, responsible for up to 20% of the annual global CO
2
fixation. The evolution of a CO
2
-concentrating mechanism (CCM) allowed diatoms to overcome a number of serious constraints on photosynthesis in the marine environment, particularly low [CO
2
]
aq
in seawater relative to concentrations required by the CO
2
fixing enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO), which is partly due to the slow diffusion rate of CO
2
in water and a limited CO
2
formation rate from

in seawater. Diatoms use two alternative strategies to take up dissolved inorganic carbon (DIC) from the environment: one primarily relies on the direct uptake of

through plasma-membrane type solute carrier (SLC) 4 family

transporters and the other is more reliant on passive diffusion of CO
2
formed by an external carbonic anhydrase (CA). Bicarbonate taken up into the cytoplasm is most likely then actively transported into the chloroplast stroma by SLC4-type transporters on the chloroplast membrane system. Bicarbonate in the stroma is converted into CO
2
only in close proximity to RubisCO preventing unnecessary CO
2
leakage. CAs play significant roles in mobilizing DIC as it is progressively moved towards the site of fixation. However, the evolutionary types and subcellular locations of CAs are not conserved between different diatoms, strongly suggesting that this DIC mobilization strategy likely evolved multiple times with different origins. By contrast, the recent discovery of the thylakoid luminal θ-CA indicates that the strategy to supply CO
2
to RubisCO in the pyrenoid may be very similar to that of green algae, and strongly suggests convergent coevolution in CCM function of the thylakoid lumen not only among diatoms but among eukaryotic algae in general. In this review, both experimental and corresponding theoretical models of the diatom CCMs are discussed.

This article is part of the themed issue ‘The peculiar carbon metabolism in diatoms’.
Structure and properties of oil bodies in diatoms
Authors: Maeda Yoshiaki , Nojima Daisuke , Yoshino Tomoko , Tanaka Tsuyoshi
Published: July 2017

Diatoms accumulate triacylglycerols in spherical organelles called oil bodies when exposed to nutrient deprivation conditions. Oil body biology in diatoms has attracted significant attention due to the complexity of the intracellular organelles and the unique combination of genes generated by the evolutionary history of secondary endosymbiosis. The demand for biofuel production has further increased the interest in and importance of a better understanding of oil body biology in diatoms, because it could provide targets for genetic engineering to further enhance their promising lipid accumulation. This review describes recent progress in studies of the structure and properties of diatom oil bodies. Firstly, the general features of diatom oil bodies are described, in particular, their number, size and morphology, as well as the quantity and quality of lipids they contain. Subsequently, the diatom oil body-associated proteins, which were recently discovered through oil body proteomics, are introduced. Then, the metabolic pathways responsible for the biogenesis and degradation of diatom oil bodies are summarized. During biogenesis and degradation, oil bodies interact with other organelles, including chloroplasts, the endoplasmic reticulum and mitochondria, suggesting their dynamic nature in response to environmental changes. Finally, the functions of oil bodies in diatoms are discussed.

This article is part of the themed issue ‘The peculiar carbon metabolism in diatoms’.
Genetic and metabolic engineering in diatoms
Authors: Huang Weichao , Daboussi Fayza
Published: July 2017

Diatoms have attracted considerable attention due to their success in diverse environmental conditions, which probably is a consequence of their complex origins. Studies of their metabolism will provide insight into their adaptation capacity and are a prerequisite for metabolic engineering. Several years of investigation have led to the development of the genome engineering tools required for such studies, and a profusion of appropriate tools is now available for exploring and exploiting the metabolism of these organisms. Diatoms are highly prized in industrial biotechnology, due to both their richness in natural lipids and carotenoids and their ability to produce recombinant proteins, of considerable value in diverse markets. This review provides an overview of recent advances in genetic engineering methods for diatoms, from the development of gene expression cassettes and gene delivery methods, to cutting-edge genome-editing technologies. It also highlights the contributions of these rapid developments to both basic and applied research: they have improved our understanding of key physiological processes; and they have made it possible to modify the natural metabolism to favour the production of specific compounds or to produce new compounds for green chemistry and pharmaceutical applications.

This article is part of the themed issue ‘The peculiar carbon metabolism in diatoms’.
Management coaching with performance templates to stimulate self-regulated learning
Authors: Lyons Paul , Bandura Randall P.
Published: July 2017

Purpose

Much has been written about self-regulated learning (SRL) (including mind-sets) in psychology and education, but little research is found in the HRD or training literature regarding the stimulation of this learning. This paper aims to present a practical training tool, performance templates (P-T), to demonstrate how a line manager may assist employees improve their problem-solving skills as well as stimulate SRL.

Design/methodology/approach

Presented are literature reviews and assessments of the areas of: line manager in coaching role, SRL theory and the phases of SRL in action. Following is a detailed explanation and demonstration of the P-T method. Finally, the efficacy of PT is examined and constraints are noted.

Findings

Demonstrated in the paper is how a line manager may function as the key actor in assisting employees to become more effective self-regulating learners and problem-solvers. The method presented can stimulate employee motivation and help employees to internalize self-regulating learning processes. All of this should help employees become more growth-oriented, self-confident and goal-directed participants in organizational life.

Originality/value

Rather than simply discuss what SRL is about, this paper provides an effective tool, P-T, for use in the stimulation and direction of SLR. The use of the tool also helps organization participants to achieve progress on some current problems.
Complexity and the triple bottom line: an information-processing perspective
Authors: Wiengarten Frank , Ahmed Muhammad Usman , Longoni Annachiara , Pagell Mark , Fynes Brian
Published: July 2017

Purpose

The purpose of this paper is to empirically investigate the impact of complexity on the triple bottom line by applying information-processing theory. Specifically, the paper assesses the impact of internal manufacturing complexity on environmental, social, and financial performance. Furthermore, the paper assesses the moderating role of connectivity and shared schema in reducing the potential negative impact of complexity on performance.

Design/methodology/approach

Multi-country survey data collected through the Global Manufacturing Research Group were utilized to test the hypotheses. The authors used structural equation modeling to test the measurement and initial structural model. Furthermore, to test the proposed moderating hypotheses, the authors applied the latent moderated structural equations approach.

Findings

The results indicate that while complexity has a negative impact on environmental and social performance, it does not significantly affect financial performance. Furthermore, this negative impact can be reduced, to some extent, through connectivity; however, shared schema does not significantly impact on the complexity-performance relationship.

Originality/value

This study presents a comprehensive analysis of the impact of complexity on sustainability. Furthermore, it provides managerial applications as it proposes specific tools to deal with the potential negative influences of complexity.
The reconfiguration of service production systems in response to offshoring
Authors: Brandl Kristin , Mol Michael J. , Petersen Bent
Published: July 2017

Purpose

A service production system has a structure composed of task execution, agents performing tasks and a resulting service output. The purpose of this paper is to understand how such a service production system changes as a consequence of offshoring.

Design/methodology/approach

Drawing on practice theory, the paper investigates how offshoring leads to reconfiguration of the service production system. Through a multiple case methodology, the authors demonstrate how agents and structures interact during reconfiguration.

Findings

The paper analyses the reconfiguration of components of a service production system in response to change ignited by offshoring. The authors find recurring effects between structures that enable and constrain agents and agents who shape the structure of the production system.

Research limitations/implications

The paper offers a novel contribution to the service operations management literature by applying practice theory. Moreover, the authors propose a detailed, activity-driven view of service production systems and service offshoring. The authors contribute to practice theory by extending its domain to operations management.

Practical implications

Service production systems have the ability to self-correct any changes inflicted through offshoring of the systems, which helps firms that offshore.

Originality/value

The paper is aimed at service professionals and offshoring managers and proposes a novel presentation of the service production system with a description of how it responds to offshoring. The authors contribute to theory by applying practice theory to the fields of service operations management and offshoring.