bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of bendamustine in combination with ofatumumab in patients with relapsed or refractory marginal zone B‐cell lymphomas
Authors: Vannata Barbara , Vanazzi Anna , Negri Mara , Liptrott Sarah Jayne , Bartosek Anna Amalia , Miani Monica , Di Sanzo Alessandro , Cavalli Franco , Zucca Emanuele , Stathis Anastasios 
Published: October 2020

AbstractMarginal zone lymphomas (MZLs) are indolent yet incurable lymphomas with frequent relapses following therapy. For patients with relapsed/refractory disease, no standard therapies exist. Here we report results of an exploratory phase II study aimed at assessing the efficacy and safety of the alkylator agent bendamustine in combination with the second‐generation anti‐CD20 monoclonal antibody, ofatumumab, in patients with relapsed or refractory MZL. Patients with MZL and previously treated with at least one line of systemic therapy were eligible. Treatment consisted in bendamustine (90 mg/m2 on days 1 and 2) and ofatumumab (1000 mg on day 1) in 28‐day cycles for up to six cycles. Sixteen patients were included in the trial. In one patient, the diagnosis was revised after two cycles of treatment and was excluded from the efficacy analysis. Among 15 patients with MZL, 14 were evaluable for response: the overall and complete response rates were 92.9% and 57.1%, respectively. The median duration of response was 30.4 months (95% confidence interval [CI], 15.5 –not estimable) and 2‐years progression‐free survival 77% (95% CI, 43%–92%). Fifteen patients (94%) experienced grade 3–4 adverse events. Toxicity was mostly hematological. Neutropenia grade ≥3 was recorded in 27% of patients, lymphocytopenia in 93%, and infections and febrile neutropenia each in 13%. One patient discontinued treatment due to myocardial infarction; no treatment‐related deaths occurred. The combination of bendamustine with ofatumumab was active with an acceptable toxicity profile in this small phase II trial and can be considered for further investigation in relapsed/refractory MZL patients.
The influence of the learning health system to address the COVID‐19 pandemic: An examination of early literature
Authors: Douthit Brian J. 
Published: October 2020

AbstractIntroductionThe COVID‐19 pandemic has demanded immediate response from healthcare systems around the world. The learning health system (LHS) was created with rapid uptake of the newest evidence in mind, making it essential in the face of a pandemic. The goal of this review is to gain knowledge on the initial impact of the LHS on addressing the COVID‐19 pandemic.MethodsPubMed, Scopus and the Duke University library search tool were used to identify current literature regarding the intersection of the LHS and the COIVD‐19 pandemic. Articles were reviewed for their purpose, findings and relation to each component of the LHS.ResultsTwelve articles were included in the review. All stages of the LHS were addressed from this sample. Most articles addressed some component of interoperability. Articles that interpreted data unique to COVID‐19 and demonstrated specific tools and interventions were least common.ConclusionsGaps in interoperability are well known and unlikely to be solved in the coming months. Collaboration between health systems, researchers, governments and professional societies is needed to support a robust LHS which grants the ability to rapidly adapt to global emergencies.
Mothers' and children's depression is linked through children's perceptions of attachment security
Authors: Hughes Jeffrey L. , Morrow Kayley E. , Spears Shantel K. , Gentzler Amy L. 
Published: October 2020

AbstractThis study investigated how mothers' depressive symptoms were related to their children's depressive symptoms through children's perceived attachment security to their mother. Ninety‐six mothers reported on their depressive symptoms. Children reported on their depressive symptoms and their attachment security with their mothers. The results indicated that children's perception of security with their mothers indirectly linked mothers' depressive symptoms to their children's depressive symptoms. Furthermore, this indirect association was moderated by child's sex because only girls, whose mothers reported higher depressive symptoms, reported lower perceived attachment security. This study advances the literature on mechanisms explaining how mothers' depressive symptoms are related to their children's depressive symptoms, which have critical implications for the prevention and intervention of child and adolescent depression.Highlights
Mothers' depressive symptoms were related to children's depressive symptoms through children's perceptions of mother–child attachment security
One path in the indirect relation was moderated by child's sex such that maternal depression was associated with a less secure perceived attachment relationship for female youth but not male youth
Child depression interventions may be improved by targeting attachment relationships, with particular attention for daughters of depressed mothers
Lymphocyte‐activation gene 3 expression associates with poor prognosis and immunoevasive contexture in Epstein‐Barr virus‐positive and MLH1‐defective gastric cancer patients
Authors: Lv Kunpeng , Li Ruochen , Cao Yifan , Gu Yun , Liu Xin , He Xudong , Jin Kaifeng , Fang Hanji , Fei Yuchao , Shi Mingsu , Liu Hao , Li He , He Hongyong , Lin Chao , Zhang Heng , Xu Jiejie 
Published: October 2020

AbstractLymphocyte activation gene 3 (LAG‐3) is a transmembrane immune checkpoint that facilitates immune escape via suppressing T‐cell‐mediated anti‐tumor immunity. The role of LAG‐3 in gastric cancer is little known. Consequently, we assessed the clinical significance of LAG‐3 in gastric cancer. In our study, patients with gastric cancer from Zhongshan Hospital (n = 464) and data from the Asian Cancer Research Group (n = 300) were analyzed. LAG‐3+ cell infiltration and other immune contexture in gastric cancer were detected by immunohistochemistry. Kaplan‐Meier curves and log‐rank test were used for survival analyses. Intratumoral LAG‐3+ cells mainly accumulated in Epstein‐Barr virus (EBV)‐positive (EBV subtype) and MLH1‐defective (dMLH1 subtype) gastric cancer. Furthermore, LAG‐3+ cell infiltration was strongly associated with inferior clinical outcomes in patients with these two subtypes of gastric cancer. Moreover, we found intratumoral LAG‐3+ cell high infiltration was associated with an immunoevasive contexture featured by decreased IFN‐γ+ cells and perforin‐1+ cells, but increased regulatory T cells and M2‐like macrophages in EBV/dMLH1 subtype of gastric cancer. LAG‐3 was a poor prognostic factor and might be a potential immunotherapeutic target in EBV‐positive and MLH1‐defective gastric cancer.
A case of the world’s largest renal cell carcinoma
Authors: Takeda Kotaro , Murray Gina , Vohra Nasreen , Fallon John T 
Published: October 2020

IntroductionRenal cell carcinoma is often discovered at an early stage due to the increased use of imaging studies in the current era; therefore, its presentation as a gigantic renal cell carcinoma is rarely encountered.Case presentationA 59‐year‐old male presented to our hospital due to dizziness, fatigue, and increasing abdominal distension. A computed tomography scan showed an extremely large mass occupying most of the abdomen and pelvis. Surgical resection of the mass was performed. The largely cavitary mass with fibrous capsule was 43 cm and 13.0 kg, and contained a large amount of necrotic tissue. A portion of the left kidney was identified at the periphery of the mass, indicating that the tumor was arising from the left kidney. The final pathologic diagnosis was type 1 papillary renal cell carcinoma.ConclusionTo the best of our knowledge, this tumor is the world’s largest malignant renal tumor.
Effects of short‐duration treatment of cartilage with punicalagin and genipin and the implications for treatment of osteoarthritis
Authors: Elder Steven H. , Mosher Mark L. , Jarquin Paulino , Smith Preston , Chironis Andrea 
Published: October 2020

AbstractPunicalagin (PA) not only binds type II collagen, but also blocks its MMP‐13‐mediated degradation, and genipin (GNP) is a collagen cross‐linking agent. We hypothesized that these drugs could mitigate the loss of cartilage if administered in the early phase of osteoarthritis, and experiments were designed to provide proof‐of‐concept. Porcine cartilage was exposed to both drugs in a manner designed to simulate intra‐articular (IA) injection. Based on penetration of PA into cartilage, the rate of drug diffusion was conservatively estimated at 2 μm per minute. GNP caused a measurable degree of cross‐linking, increased compressive resistance and coefficient of friction, and substantially inhibited degradation by collagenase, but not by hyaluronidase. Pre‐incubation of GNP with collagenase had no effect on enzymatic activity. PA did not cross‐link collagen nor affect the mechanical properties of cartilage. It did, however, increase resistance to degradation by collagenase and hyaluronidase. Furthermore, it reacted with collagenase in solution and inhibited its subsequent enzymatic activity. Effects of PA and GNP were not additive. The chondroprotective effect of semi‐weekly IA injections was investigated in the monoiodoacetate‐induced model of OA in rats. Quantitative histology suggested that injection of PA decreased the amount of cartilage lost compared to saline‐injected controls, and the addition of GNP made no difference. This study supports the notion that IA delivery of PA could mitigate OA‐induced cartilage erosion.
Solubilization of sodium 3‐amino‐2‐hydroxyanthraquinone‐1‐sulphonate in sodium dodecyl sulfate micelles explains its permeation in A549 human lung cancer cell
Authors: Banerjee Somenath , Roy Sanjay , Datta Arup , Mondal Palash , Mishra Monali , Perumalsamy Balaji , Thirumurugan Ramasamy , Dharumadurai Dhanasekaran , Das Saurabh , Guin Partha Sarathi 
Published: October 2020

AbstractSodium 3‐amino‐2‐hydroxyanthraquinone‐1‐sulphonate (AQS) is an analogue of the anthracycline based chemotherapeutic drugs that was prepared as a part of the reported study. As the surfactant micelles mimics the biological membrane the present study comprises the interaction of AQS with an anionic surfactant, sodium dodecyl sulfate (SDS) in aqueous media at pH 7.4 which was monitored by using UV–Visible spectroscopy. The aim of the study is to see whether the present molecule penetrates a biological membrane. Different binding parameters like binding constant, partition coefficient, and corresponding Gibbs free energies of the interaction of AQS and its distribution between aqueous media and SDS micelles were measured. The study revealed that hydrophobic interactions play the most important role in binding of AQS to SDS micelles. To see whether AQS really permeates a biological membrane and induces apoptosis, it was allowed to interact with A549 human lung cancer cells. This study established the fact that AQS results apoptosis by means of nucleation into this cell.
Parametric Approaches in Population Pharmacokinetics
Authors: Guidi Monia , Csajka Chantal , Buclin Thierry 
Published: October 2020

AbstractPopulation pharmacokinetic (popPK) approaches have spread widely throughout clinical pharmacology research, and every clinician should have some understanding of them. After a general introduction on the fundamentals and fields of application of these approaches, this review focuses on parametric popPK methods to provide the clinicians with the conceptual tools to interpret appropriately the results of parametric popPK analyses and to understand their clinical utility. The emphasis is put on the clinical questions that popPK methods are best suited to address. The basic principles of the methodology are introduced first, and then the main algorithms and reference software programs used in such analyses are presented. The description of data analysis and clinical applications of the parametric popPK approach (ie, use in simulations and therapeutic drug monitoring) are illustrated with the example of the antiretroviral drug efavirenz.
Pollen morphology of some species of the genus Cephalaria Schrad. (Caprifoliaceae) and its significance for taxonomy
Authors: Tsymbalyuk Zoya M. , Celenk Sevcan , Mosyakin Sergei L. , Nitsenko Lyudmila M. 
Published: October 2020

AbstractPalynology gives the evidence for identification and elimination of taxonomically complex genera. Pollen morphology of nine species (three subg., three sect.) of the genus Cephalaria Schrad. was studied using light microscopy and scanning electron microscopy. Pollen grains of all investigated species are triporate, suboblate to subprolate (P/E = 0.75–1.28), and large‐sized (P = 58.52 μm–114.38, E = 63.84–119.70 μm). The outline of pollen grains in equatorial view is circular or elliptic, in polar view circular, circular‐triangular, or triangular. Pores are distinct, lolongate, elliptic, or circular, with an annulus, operculum, and distinct or indistinct, wide halo surrounding the aperture. Exine sculpture is echinate‐microechinate or echinate‐microechinate‐nanoechinate. Additional diagnostic characters at the species level in Cephalaria Schrad. that can be used for the purposes of taxonomy are size of pollen grains and pores, the shape of pores, the width of the annulus, structure of the exine, dimension of echini and microechini, location of microechini, and presence/absence of nanoechini. Palynomorphological data are compared with the taxonomical classification system of investigated taxa. It is shown that pollen grains morphology of the genus Cephalaria Schrad. is similar to the pollen morphology of the genus Dipsacus L., which confirms their inclusion in the Dipsaceae tribe.
The impact of genetic counseling on women's grief and coping following termination of pregnancy for fetal anomaly
Authors: Smith Cayleen , Hashmi Syed S. , Czerwinski Jennifer , Wagner Victoria F. , Promecene Pamela , Milentijevic Irena , Ramdaney Aarti 
Published: October 2020

AbstractPregnancy termination for fetal anomaly (TFA) is a unique experience that can cause women to develop long‐term complicated grief. Although a woman's experience with her healthcare providers has been previously identified as an important factor in coping, studies have shown that many women report their health care as lacking to some extent. Given the overlap in women's needs and the practice scope of a genetic counselor (GC), this study aimed to examine how genetic counseling may impact coping and explore women's expectations of GCs pre‐ and post‐TFA. An online survey, which included the brief COPE and the short version of the Perinatal Grief Scale, was distributed among private online support groups. Appropriate statistical analysis tools, such as the Wilcoxon rank‐sum and t test, were utilized for quantitative analysis of the 124 responses, and inductive content analysis was utilized for qualitative analysis. Of those who underwent TFA within the last two years, women who saw a GC utilized active coping, planning, and positive reframing significantly more than women who did not see a GC (p = 0.001, p = 0.031, p = 0.027, respectively). GCs were perceived to have a positive impact on coping when providing information, objective care, emotional support, support resources, and follow‐up care; these practices encouraged confidence in their personal decision‐making and gave women hope for the future. This study not only identified key counseling roles for GCs prior to a TFA, but also demonstrated that genetic counseling prior to TFA may be beneficial to coping. Further studies are warranted to explore the needs of a more diverse population and to identify appropriate genetic counseling training methods to support women pursuing TFA.
Surgical mask use by healthcare personnel to prevent COVID‐19 spread in a long‐term care facility
Authors: Abe Toshikazu , Tokuda Yasuharu , Iriyama Hiroki , Iwagami Masao , Komori Akira , Sugiyama Takehiro , Tamiya Nanako 
Published: October 2020

AbstractLong‐term care facilities are a recognized high‐risk setting for severe outcomes during the coronavirus disease 2019 (COVID‐19) outbreak. This study describes a COVID‐19 outbreak in a long‐term care facility in Japan. The index case was a nurse who wore a surgical mask and used standard precautions. Of the 17 confirmed cases of COVID‐19, 14 (14/93, 15.1%) were residents and three (3/69, 4.3%) were healthcare personnel (HCP); no visitors tested positive 0 (0/22, 0.0%). Mask utilization by HCP was not much effective in preventing COVID‐19 transmission, even when interaction was not considered as being in close contact.
At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer
Authors: Luker Gary D , Yang Jinming , Richmond Ann , Scala Stefania , Festuccia Claudio , Schottelius Margret , Wester Hans-Jürgen , Zimmermann Johann 
Published: October 2020

Abstract
Signaling through chemokine receptor, C-X-C chemokine receptor type 4 (CXCR4) regulates essential processes in normal physiology, including embryogenesis, tissue repair, angiogenesis, and trafficking of immune cells. Tumors co-opt many of these fundamental processes to directly stimulate proliferation, invasion, and metastasis of cancer cells. CXCR4 signaling contributes to critical functions of stromal cells in cancer, including angiogenesis and multiple cell types in the tumor immune environment. Studies in animal models of several different types of cancers consistently demonstrate essential functions of CXCR4 in tumor initiation, local invasion, and metastasis to lymph nodes and distant organs. Data from animal models support clinical observations showing that integrated effects of CXCR4 on cancer and stromal cells correlate with metastasis and overall poor prognosis in &gt;20 different human malignancies. Small molecules, Abs, and peptidic agents have shown anticancer efficacy in animal models, sparking ongoing efforts at clinical translation for cancer therapy. Investigators also are developing companion CXCR4-targeted imaging agents with potential to stratify patients for CXCR4-targeted therapy and monitor treatment efficacy. Here, pre-clinical studies demonstrating functions of CXCR4 in cancer are reviewed.
Evolutionary and functional substitution of extrinsic musculature in Solifugae (Arachnida)
Authors: Runge Jens , Wirkner Christian S. 
Published: October 2020

AbstractThe locomotory system of Solifugae is distinct from that of other Arachnida in several ways. Only three pairs of legs are involved in locomotion, while the first pair function as sensory appendages. Morphologically, the proximal region of the locomotory system in Solifugae is characterized by fused coxae. Within the prosoma of Solifugae, an endosternite is missing: in other Arachnida, this endosternite serves as the proximal attachment site for a portion of the extrinsic musculature. How then do these skeletal modifications influence the muscular anatomy in the proximal region of the locomotory system? To answer this question, we studied the skeletomuscular anatomy of Galeodes granti at the interface between the prosoma and legs, reinvestigating the complex muscular anatomy of this body region for the first time in over 80 years and—for the first time—using detailed micro‐computed tomography scans to analyze the skeletomuscular morphology. Specimens of three further species were checked for comparison. The analysis revealed differences in the number and composition of coxa‐trochanter muscles in each of the four pairs of legs. These are compared in the light of serial homology. The comparison between the proximal locomotory system of Solifugae and that of other Arachnida unveils a series of analogies. Primarily, the coxa‐trochanter joint is the most proximal joint to move the leg relative to the prosoma. Therefore, we argue that from a morpho‐functional point of view, the coxa‐trochanter muscles in Solifugae should be considered secondary extrinsic musculature. Thus, the legs gain a stable, articulated joint in the most proximal region of the leg to the prosoma, which might be advantageous for agile locomotion.
Increased occurrence of pathological mitochondria in astrocytic perivascular endfoot processes and neurons of idiopathic intracranial hypertension
Authors: Eide Per Kristian , Hasan‐Olive Md Mahdi , Hansson Hans‐Arne , Enger Rune 
Published: October 2020

AbstractIdiopathic intracranial hypertension (IIH) primarily affects fertile, overweight women, and presents with the symptoms of raised intracranial pressure. The etiology is unknown but has been thought to relate to cerebrospinal fluid disturbance or cerebral venous stenosis. We have previously found evidence that IIH is also a disease of the brain parenchyma, evidenced by alterations at the neurogliovascular interface, including astrogliosis, pathological changes in the basement membrane and pericytes, and alterations of perivascular aquaporin‐4. The aim of this present electron microscopic study was to examine whether mitochondria phenotype was changed in IIH, particularly focusing on perivascular astrocytic endfeet and neurons (soma and pre‐ and postsynaptic terminals). Cortical brain biopsies of nine reference individuals and eight IIH patients were analyzed for subcellular distribution and phenotypical features of mitochondria using transmission electron microscopy. We found significantly increased prevalence of pathological mitochondria and reduced number of normal mitochondria in astrocytic endfeet of IIH patients. The degree of astrogliosis correlated negatively with the number of normal mitochondria in astrocytic endfoot processes. Moreover, we found significantly increased number of pathological mitochondria in pre‐ and postsynaptic neuronal terminals, as well as significantly shortened distance between mitochondria and endoplasmic reticulum contacts. Finally, the length of postsynaptic density, a marker of synaptic strength, was on average reduced in IIH. The present data provide evidence of pathological mitochondria in perivascular astrocytes endfeet and neurons of IIH patients, highlighting that impaired metabolism at the neurogliovascular interface may be a facet of IIH.
Expanded practice in rural community pharmacy in Australia: pharmacists’ perspectives
Authors: Taylor Selina , Cairns Alice , Glass Beverley 
Published: October 2020

AbstractBackgroundPharmacists internationally have successfully expanded their role to provide service delivery to remote rural communities.AimThis study evaluated Australian rural community pharmacists’ perspectives of expanded services, to identify priorities, areas of concern, enablers and barriers to their implementation.MethodA self‐administered questionnaire was distributed to rural and remote Australian (all states and territories) pharmacists between September and December 2019; respondents were asked to rank health issues and the expanded pharmacy services that could potentially address these issues in their communities. Questions were also included to evaluate health service accessibility, skills/knowledge, workspace limitations, time and support for the implementation of these services. Potential associations between demographic factors and responses were also assessed.ResultsOf the 92 returned responses analysed, the top three heath concerns were: Mental health, Cardiovascular disease and Diabetes. Depression screening/referral, diabetes management and vaccinations were the top three areas rated for expanded services. There was agreement (90%; 83/92) that pharmacists had the skills and knowledge for implementation, while time and space were reported as barriers for 50% (46/92) and 25% (23/92) of pharmacists, respectively. The majority of the pharmacists (80%; 74/92) felt services were not easily accessible, and all (92/92, 100%) agreed that service provision would improve community health outcomes.ConclusionRural pharmacists were supportive of the delivery of expanded pharmacy services, describing improved health outcomes and increased access to health services as potential benefits. Successful implementation of these expanded services would require both an understanding of pharmacist resources available and local community health needs.