bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions of HIV and Antiretroviral Therapy With Neutrophils and Platelets
Authors: Madzime Morris , Rossouw Theresa M. , Theron Annette J. , Anderson Ronald , Steel Helen C.
Published: March 2021

Neutrophils are important components of the innate immune system that mediate pathogen defense by multiple processes including phagocytosis, release of proteolytic enzymes, production of reactive oxygen species, and neutrophil extracellular trap formation. Abnormalities of neutrophil count and function have been described in the setting of HIV infection, with the majority of antiretroviral agents (ARVs), excluding zidovudine, having been reported to correct neutropenia. Questions still remain, however, about their impact on neutrophil function, particularly the possibility of persistent neutrophil activation, which could predispose people living with HIV to chronic inflammatory disorders, even in the presence of virally-suppressive treatment. In this context, the effects of protease inhibitors and integrase strand transfer inhibitors, in particular, on neutrophil function remain poorly understood and deserve further study. Besides mediating hemostatic functions, platelets are increasingly recognized as critical role players in the immune response against infection. In the setting of HIV, these cells have been found to harbor the virus, even in the presence of antiretroviral therapy (ART) potentially promoting viral dissemination. While HIV-infected individuals often present with thrombocytopenia, they have also been reported to have increased platelet activation, as measured by an upregulation of expression of CD62P (P-selectin), CD40 ligand, glycoprotein IV, and RANTES. Despite ART-mediated viral suppression, HIV-infected individuals reportedly have sustained platelet activation and dysfunction. This, in turn, contributes to persistent immune activation and an inflammatory vascular environment, seemingly involving neutrophil-platelet-endothelium interactions that increase the risk for development of comorbidities such as cardiovascular disease (CVD) that has become the leading cause of morbidity and mortality in HIV-infected individuals on treatment, clearly underscoring the importance of unraveling the possible etiologic roles of ARVs. In this context, abacavir and ritonavir-boosted lopinavir and darunavir have all been linked to an increased risk of CVD. This narrative review is therefore focused primarily on the role of neutrophils and platelets in HIV transmission and disease, as well as on the effect of HIV and the most common ARVs on the numbers and functions of these cells, including neutrophil-platelet-endothelial interactions.
Lung Functioning and Inflammation in a Mouse Model of Systemic Juvenile Idiopathic Arthritis
Authors: Malengier-Devlies Bert , Decaesteker Tatjana , Dekoster Kaat , Vanstapel Arno , Ahmadzadeh Kourosh , Poosti Fariba , Mitera Tania , Seldeslachts Laura , Verbeken Erik , Wouters Carine , Vande Velde Greetje , Vanoirbeek Jeroen , Matthys Patrick
Published: March 2021

Systemic juvenile idiopathic arthritis (sJIA) is an immune disorder characterized by fever, skin rash, arthritis and splenomegaly. Recently, increasing number of sJIA patients were reported having lung disease. Here, we explored lung abnormalities in a mouse model for sJIA relying on injection of IFN-γ deficient (IFN-γ KO) mice with complete Freund's adjuvant (CFA). Monitoring of lung changes during development of sJIA using microcomputer tomography revealed a moderate enlargement of lungs, a decrease in aerated and increase in non-aerated lung density. When lung function and airway reactivity to methacholine was assessed, gender differences were seen. While male mice showed an increased tissue hysteresivity, female animals were characterized by an increased airway hyperactivity, mirroring ongoing inflammation. Histologically, lungs of sJIA-like mice showed subpleural and parenchymal cellular infiltrates and formation of small granulomas. Flow cytometric analysis identified immature and mature neutrophils, and activated macrophages as major cell infiltrates. Lung inflammation in sJIA-like mice was accompanied by augmented expression of IL-1β and IL-6, two target cytokines in the treatment of sJIA. The increased expression of granulocyte colony stimulating factor, a potent inducer of granulopoiesis, in lungs of mice was striking considering the observed neutrophilia in patients. We conclude that development of sJIA in a mouse model is associated with lung inflammation which is distinct to the lung manifestations seen in sJIA patients. Our observations however underscore the importance of monitoring lung disease during systemic inflammation and the model provides a tool to explore the underlying mechanism of lung pathology in an autoinflammatory disease context.
Five Questions to Understand Epistemology and Its Influence on Integrative Marine Research
Authors: Moon Katie , Cvitanovic Christopher , Blackman Deborah A. , Scales Ivan R. , Browne Nicola K.
Published: March 2021

Developing solutions to the complex and uncertain problems facing marine and coastal social-ecological ecosystems requires new forms of knowledge production and integration. While progress has been made both in terms of successfully producing integrated marine research and connecting that knowledge to decision-makers, a number of significant challenges remain that prevent the routine development and implementation of successful integrated research practice. Based on our own experiences as social researchers working within interdisciplinary research teams, we contend that one of the main barriers to successful integrative marine research relates to understanding, and where possible reconciling, the different epistemologies that unpin how knowledge is created or discovered in different disciplines. We therefore aim to provide an accessible introduction to the concept of epistemology, with a focus on its importance and influence to integrated marine research practice. Specifically, we present and discuss five questions of research design that relate to epistemology in integrative research practices: (1) What is the object of study we seek to create knowledge about; (2) how do we create knowledge; (3) who accepts knowledge as ‘true’ and how?; (4) how do we determine the epistemology underpinning marine science; and (5) what are the implications of epistemology for applied integrative marine science? We demonstrate the application of each question through a hypothetical case study of marine restoration, focusing on coral transplanting. Finally, we offer readers a simple heuristic to guide them, irrespective of career stage or discipline, to understand and account for epistemology when participating in integrative marine research practices.
A Novel Normalized Cross-Correlation Speckle-Tracking Ultrasound Algorithm for the Evaluation of Diaphragm Deformation
Authors: Ye Xiong , Liu Zhi , Ma Ying , Song Ye , Hu Lihua , Luo Jianwen , Xiao Hui
Published: March 2021

Objectives: To develop a two-dimensional normalized cross-correlation (NCC)-based ultrasonic speckle-tracking algorithm for right diaphragm deformation analysis.

Methods: Six healthy and eight mechanical ventilation patients were enrolled in this study. Images were acquired by a portable ultrasound system in three sections. DICOM data were processed with NCC to obtain the interframe/cumulative vertical and horizontal displacements, as well as the global strain of the right diaphragm, with continuous tracking and drift correction.

Results: The NCC algorithm can track the contraction and relaxation of the right diaphragm by following the respiratory movement continuously. For all three sections, the interframe and accumulated horizontal displacements were both significantly larger than the corresponding vertical displacements (interframe p values: 0.031, 0.004, and 0.000; cumulative p values: 0.039, 0.001, and <0.0001). For the global strain of the right diaphragm, there was no significant difference between each pair of sections (all p > 0.05), regardless of whether the horizontal interval of the initial diaphragm point was 1, 3, 5, or 10 times in the sampling interval.

Conclusions: This study developed a novel diaphragm deformation ultrasound imaging method. This method can be used to estimate the diaphragm interframe/accumulated displacement in the horizontal and vertical directions and the global strain on three different imaging planes, and it was found that the strain was not sensitive to the imaging plane.
Microbiome Composition and Function in Aquatic Vertebrates: Small Organisms Making Big Impacts on Aquatic Animal Health
Authors: Sehnal Ludek , Brammer-Robbins Elizabeth , Wormington Alexis M. , Blaha Ludek , Bisesi Joe , Larkin Iske , Martyniuk Christopher J. , Simonin Marie , Adamovsky Ondrej
Published: March 2021

Aquatic ecosystems are under increasing stress from global anthropogenic and natural changes, including climate change, eutrophication, ocean acidification, and pollution. In this critical review, we synthesize research on the microbiota of aquatic vertebrates and discuss the impact of emerging stressors on aquatic microbial communities using two case studies, that of toxic cyanobacteria and microplastics. Most studies to date are focused on host-associated microbiomes of individual organisms, however, few studies take an integrative approach to examine aquatic vertebrate microbiomes by considering both host-associated and free-living microbiota within an ecosystem. We highlight what is known about microbiota in aquatic ecosystems, with a focus on the interface between water, fish, and marine mammals. Though microbiomes in water vary with geography, temperature, depth, and other factors, core microbial functions such as primary production, nitrogen cycling, and nutrient metabolism are often conserved across aquatic environments. We outline knowledge on the composition and function of tissue-specific microbiomes in fish and marine mammals and discuss the environmental factors influencing their structure. The microbiota of aquatic mammals and fish are highly unique to species and a delicate balance between respiratory, skin, and gastrointestinal microbiota exists within the host. In aquatic vertebrates, water conditions and ecological niche are driving factors behind microbial composition and function. We also generate a comprehensive catalog of marine mammal and fish microbial genera, revealing commonalities in composition and function among aquatic species, and discuss the potential use of microbiomes as indicators of health and ecological status of aquatic ecosystems. We also discuss the importance of a focus on the functional relevance of microbial communities in relation to organism physiology and their ability to overcome stressors related to global change. Understanding the dynamic relationship between aquatic microbiota and the animals they colonize is critical for monitoring water quality and population health.
Comprehensive Substrate-Based Exploration of Probiotics From Undistilled Traditional Fermented Alcoholic Beverage ‘Lugri’
Authors: Baliyan Neha , Dindhoria Kiran , Kumar Aman , Thakur Aman , Kumar Rakshak
Published: March 2021

Cereal-based traditional fermented beverages (TFBs) are prevalent among India’s ethnic community, and lugri is one such TFB popular among the tribal people of the Lahaul valley in North-Western Himalaya. Previous studies have reported that lugri harbors probiotics and contains amino acids and vitamins but comprehensive substrate-specific exploration of lugri for probiotic attributes is unexplored. The present study selected three substrate-based lugri (wheat, rice, and barley) to study their biochemical properties and explore potential probiotics. This study screened the best probiotic strains for antioxidant studies and the fermentative process. A biochemical analysis determined that rice-based lugri had a higher alcohol content, electric conductivity, crude protein, and lower pH than barley and wheat-based lugri. A total of 134 distinct morphotypes were screened, and 43 strains were selected based on their qualitatively superior acid and bile tolerance. Rice-based undistilled lugri harbored the most probiotics, with 22 out of 43 strains isolated. All 43 bacterial isolates exhibited properties like cell surface hydrophobicity, cell-auto aggregation, β-galactosidase, and exopolysaccharide production, supporting them as possible probiotics. Based on antibiotic susceptibility, hemolytic activity, and biofilm formation, all the bacterial strains were found to be non-pathogenic. Taxonomically, they ranged among eight distinct genera and 10 different species. Statistically, 12 isolates were found to be the most promising probiotic, and eight strains were isolated from rice-based undistilled lugri. Furthermore, the antioxidant activity of the promising isolates was tested, based on free-radical scavenging ability toward 2,2-diphenyl-1-picrylhydrazyl (4.39–16.41%) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (15.29–57.74%). The strain Lacticaseibacillus paracasei LUL:01 showed the best antioxidant activity and probiotic attributes, and hence was used for the production of fermented milk. The strain LUL:01 fermented the sterile milk within 18 h, and the viable count remained above the legal requirement of 6 log10 CFU/ml during 28 days storage at 4°C. The strain represents a suitable candidate for applying probiotic functional food formulation with several health benefits.
Wolbachia Endosymbionts of Fleas Occur in All Females but Rarely in Males and Do Not Show Evidence of Obligatory Relationships, Fitness Effects, or Sex-Distorting Manipulations
Authors: Flatau Ron , Segoli Michal , Hawlena Hadas
Published: March 2021

The widespread temporal and spatial persistence of endosymbionts in arthropod host populations, despite potential conflicts with their hosts and fluctuating environmental conditions, is puzzling. Here, we disentangled three main mechanisms that are commonly proposed to explain such persistence, namely, obligatory relationships, in which the host is fully dependent on its endosymbiont, fitness advantages conferred by the endosymbiont, and reproductive manipulations imposed by the endosymbiont. Our model system reflects an extreme case, in which the Wolbachia endosymbiont persists in all female flea hosts but rarely in male ones. We cured fleas of both sexes of Wolbachia but found no indications for either lower reproduction, offspring survival, or a change in the offspring sex ratio, compared to Wolbacia-infected fleas. These results do not support any of the suggested mechanisms. We highlight future directions to advance our understanding of endosymbiont persistence in fleas, as well as in other model systems, with extreme sex-differences in endosymbiont persistence. Insights from such studies are predicted to shed light on the evolution and ecology of arthropod-endosymbiont interactions in nature.
Influence of iTBS on the Acute Neuroplastic Change After BCI Training
Authors: Ding Qian , Lin Tuo , Wu Manfeng , Yang Wenqing , Li Wanqi , Jing Yinghua , Ren Xiaoqing , Gong Yulai , Xu Guangqing , Lan Yue
Published: March 2021

Objective: Brain-computer interface (BCI) training is becoming increasingly popular in neurorehabilitation. However, around one third subjects have difficulties in controlling BCI devices effectively, which limits the application of BCI training. Furthermore, the effectiveness of BCI training is not satisfactory in stroke rehabilitation. Intermittent theta burst stimulation (iTBS) is a powerful neural modulatory approach with strong facilitatory effects. Here, we investigated whether iTBS would improve BCI accuracy and boost the neuroplastic changes induced by BCI training.

Methods: Eight right-handed healthy subjects (four males, age: 20–24) participated in this two-session study (BCI-only session and iTBS+BCI session in random order). Neuroplastic changes were measured by functional near-infrared spectroscopy (fNIRS) and single-pulse transcranial magnetic stimulation (TMS). In BCI-only session, fNIRS was measured at baseline and immediately after BCI training. In iTBS+BCI session, BCI training was followed by iTBS delivered on the right primary motor cortex (M1). Single-pulse TMS was measured at baseline and immediately after iTBS. fNIRS was measured at baseline, immediately after iTBS, and immediately after BCI training. Paired-sample t-tests were used to compare amplitudes of motor-evoked potentials, cortical silent period duration, oxygenated hemoglobin (HbO2) concentration and functional connectivity across time points, and BCI accuracy between sessions.

Results: No significant difference in BCI accuracy was detected between sessions (p > 0.05). In BCI-only session, functional connectivity matrices between motor cortex and prefrontal cortex were significantly increased after BCI training (p's < 0.05). In iTBS+BCI session, amplitudes of motor-evoked potentials were significantly increased after iTBS (p's < 0.05), but no change in HbO2 concentration or functional connectivity was observed throughout the whole session (p's > 0.05).

Conclusions: To our knowledge, this is the first study that investigated how iTBS targeted on M1 influences BCI accuracy and the acute neuroplastic changes after BCI training. Our results revealed that iTBS targeted on M1 did not influence BCI accuracy or facilitate the neuroplastic changes after BCI training. Therefore, M1 might not be an effective stimulation target of iTBS for the purpose of improving BCI accuracy or facilitate its effectiveness; other brain regions (i.e., prefrontal cortex) are needed to be further investigated as potentially effective stimulation targets.
Adjudicating Between Local and Global Architectures of Predictive Processing in the Subcortical Auditory Pathway
Authors: Tabas Alejandro , von Kriegstein Katharina
Published: March 2021

Predictive processing, a leading theoretical framework for sensory processing, suggests that the brain constantly generates predictions on the sensory world and that perception emerges from the comparison between these predictions and the actual sensory input. This requires two distinct neural elements: generative units, which encode the model of the sensory world; and prediction error units, which compare these predictions against the sensory input. Although predictive processing is generally portrayed as a theory of cerebral cortex function, animal and human studies over the last decade have robustly shown the ubiquitous presence of prediction error responses in several nuclei of the auditory, somatosensory, and visual subcortical pathways. In the auditory modality, prediction error is typically elicited using so-called oddball paradigms, where sequences of repeated pure tones with the same pitch are at unpredictable intervals substituted by a tone of deviant frequency. Repeated sounds become predictable promptly and elicit decreasing prediction error; deviant tones break these predictions and elicit large prediction errors. The simplicity of the rules inducing predictability make oddball paradigms agnostic about the origin of the predictions. Here, we introduce two possible models of the organizational topology of the predictive processing auditory network: (1) the global view, that assumes that predictions on the sensory input are generated at high-order levels of the cerebral cortex and transmitted in a cascade of generative models to the subcortical sensory pathways; and (2) the local view, that assumes that independent local models, computed using local information, are used to perform predictions at each processing stage. In the global view information encoding is optimized globally but biases sensory representations along the entire brain according to the subjective views of the observer. The local view results in a diminished coding efficiency, but guarantees in return a robust encoding of the features of sensory input at each processing stage. Although most experimental results to-date are ambiguous in this respect, recent evidence favors the global model.
Brain Functional Mechanisms Determining the Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation in Primary Insomnia
Authors: Wu Xiao , Zhang Yue , Luo Wen-ting , Mai Run-ru , Hou Xiao-yan , Xia Zi-qiang , Xu Bi-yun , Liu Bo
Published: March 2021

Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective in the treatment of primary insomnia (PI); however, its efficacy varies considerably across individuals for reasons that are unclear. In order to clarify the underlying mechanisms, this study investigated the effects of taVNS on spontaneous neuronal activity and autonomic nervous system function by functional magnetic resonance imaging (fMRI) and measurement of heart rate variability (HRV), respectively, in patients with PI. Forty patients with PI were divided into effective (group A) and ineffective (group B) groups based on their response to taVNS as determined by Pittsburgh Sleep Quality Index score reduction rate (group A ≥ 25% and group B < 25%). Spontaneous neuronal activity was measured by fractional amplitude of low-frequency fluctuations (fALFF) and HRV values and was compared between the two groups as well as beforevsafter taVNS. We then analyzed the correlations among efficacy of taVNS for 4 weeks, the fALFF and HRV values during continuous taVNS state. The results showed that the HRV parameter values (i.e., root mean square of successive differences, percentage of adjacent NN intervals differing by >50 ms, and high frequency) of group A were higher than those of group B during continuous taVNS state. In the fMRI scan, the fALFF values of the right cerebellum, right medial superior frontal gyrus, and bilateral supplementary motor area—which belong to the sensorimotor network (SMN)—were lower in group A than in group B during continuous taVNS state. The correlation analysis revealed that the efficacy of continuous taVNS and HRV and fALFF values were interrelated. These findings demonstrate that differential regulation of the SMN by the autonomic nervous system may be responsible for inter-individual variations in the efficacy of taVNS and suggest that HRV and fALFF are potential biomarkers for predicting PI patients’ response to taVNS treatment.
Activities of the Right Temporo-Parieto-Occipital Junction Reflect Spatial Hearing Ability in Cochlear Implant Users
Authors: Schäfer Eusebia , Vedoveli Ana-Elena , Righetti Giulia , Gamerdinger Philipp , Knipper Marlies , Tropitzsch Anke , Karnath Hans-Otto , Braun Christoph , Li Hegner Yiwen
Published: March 2021

Spatial hearing is critical for us not only to orient ourselves in space, but also to follow a conversation with multiple speakers involved in a complex sound environment. The hearing ability of people who suffered from severe sensorineural hearing loss can be restored by cochlear implants (CIs), however, with a large outcome variability. Yet, the causes of the CI performance variability remain incompletely understood. Despite the CI-based restoration of the peripheral auditory input, central auditory processing might still not function fully. Here we developed a multi-modal repetition suppression (MMRS) paradigm that is capable of capturing stimulus property-specific processing, in order to identify the neural correlates of spatial hearing and potential central neural indexes useful for the rehabilitation of sound localization in CI users. To this end, 17 normal hearing and 13 CI participants underwent the MMRS task while their brain activity was recorded with a 256-channel electroencephalography (EEG). The participants were required to discriminate between the probe sound location coming from a horizontal array of loudspeakers. The EEG MMRS response following the probe sound was elicited at various brain regions and at different stages of processing. Interestingly, the more similar this differential MMRS response in the right temporo-parieto-occipital (TPO) junction in CI users was to the normal hearing group, the better was the spatial hearing performance in individual CI users. Based on this finding, we suggest that the differential MMRS response at the right TPO junction could serve as a central neural index for intact or impaired sound localization abilities.
Evaluating the Impact of Goal Setting on Improving Diet Quality in Chronic Kidney Disease
Authors: Chan Chi H. , Conley Marguerite , Reeves Marina M. , Campbell Katrina L. , Kelly Jaimon T.
Published: March 2021

Background: Improving diet quality in chronic kidney disease (CKD) is challenging due to a myriad of competing recommendations. Patient-centered goal setting can facilitate dietary behavior change; however, its role in improving diet quality in CKD has not been investigated.

Aim: The aim of the study is to evaluate the effects of goal setting on improving diet quality in stages 3–4 CKD.

Methods: Forty-one participants completed a 6-month dietitian-led telehealth (combined coaching calls and text messages) intervention as part of a larger RCT. Participants set one to two diet-related SMART goals and received weekly goal tracking text messages. Dietary intake was assessed using the Australian Eating Survey at baseline, 3, and 6 months, with diet quality determined using the Alternate Healthy Eating Index (AHEI).

Results: Significant improvements in AHEI (+6.9 points; 95% CI 1.2–12.7), vegetable (+1.1 serves; 95% CI 0.0–2.3) and fiber intake (+4.2 g; 95% CI 0.2–8.2) were observed at 3 months in participants setting a fruit and/or vegetable goal, compared with those who did not. However, no significant or meaningful changes were observed at 6 months. No other goal setting strategy appeared in effect on diet intake behavior or clinical outcomes in this group of CKD participants.

Conclusions: Patient-centered goal setting, particularly in relation to fruit and vegetable intake, as part of a telehealth coaching program, significantly improved diet quality (AHEI), vegetable and fiber intake over 3 months. More support may be required to achieve longer-term behavior change in stages 3–4 CKD patients.
Triple-Negative Essential Thrombocythemia: Clinical-Pathological and Molecular Features. A Single-Center Cohort Study
Authors: Cattaneo Daniele , Croci Giorgio Alberto , Bucelli Cristina , Tabano Silvia , Cannone Marta Giulia , Gaudioso Gabriella , Barbanti Maria Chiara , Barbullushi Kordelia , Bianchi Paola , Fermo Elisa , Fabris Sonia , Baldini Luca , Gianelli Umberto , Iurlo Alessandra
Published: March 2021

Lack of demonstrable mutations affecting JAK2, CALR, or MPL driver genes within the spectrum of BCR-ABL1-negative myeloproliferative neoplasms (MPNs) is currently referred to as a triple-negative genotype, which is found in about 10% of patients with essential thrombocythemia (ET) and 5–10% of those with primary myelofibrosis (PMF). Very few papers are presently available on triple-negative ET, which is basically described as an indolent disease, differently from triple-negative PMF, which is an aggressive myeloid neoplasm, with a significantly higher risk of leukemic evolution. The aim of the present study was to evaluate the bone marrow morphology and the clinical-laboratory parameters of triple-negative ET patients, as well as to determine their molecular profile using next-generation sequencing (NGS) to identify any potential clonal biomarkers. We evaluated a single-center series of 40 triple-negative ET patients, diagnosed according to the 2017 WHO classification criteria and regularly followed up at the Hematology Unit of our Institution, between January 1983 and January 2019. In all patients, NGS was performed using the Illumina Ampliseq Myeloid Panel; morphological and immunohistochemical features of the bone marrow trephine biopsies were also thoroughly reviewed. Nucleotide variants were detected in 35 out of 40 patients. In detail, 29 subjects harbored one or two variants and six cases showed three or more concomitant nucleotide changes. The most frequent sequence variants involved the TET2 gene (55.0%), followed by KIT (27.5%). Histologically, most of the cases displayed a classical ET morphology. Interestingly, prevalent megakaryocytes morphology was more frequently polymorphic with a mixture of giant megakaryocytes with hyperlobulated nuclei, normal and small sized maturing elements, and naked nuclei. Finally, in five cases a mild degree of reticulin fibrosis (MF-1) was evident together with an increase in the micro-vessel density. By means of NGS we were able to identify nucleotide variants in most cases, thus we suggest that a sizeable proportion of triple-negative ET patients do have a clonal disease. In analogy with driver genes-mutated MPNs, these observations may prevent issues arising concerning triple-negative ET treatment, especially when a cytoreductive therapy may be warranted.
The Prolactin Inducible Protein Modulates Antitumor Immune Responses and Metastasis in a Mouse Model of Triple Negative Breast Cancer
Authors: Edechi Chidalu A. , Ikeogu Nnamdi M. , Akaluka Gloria N. , Terceiro Lucas E. L. , Machado Mikayla , Salako Enitan S. , Barazandeh Aida F. , Kung Sam K. P. , Uzonna Jude E. , Myal Yvonne
Published: March 2021

The prolactin inducible protein (PIP) is expressed to varying degrees in more than 90% of breast cancers (BCs). Although high levels of PIP expression in BC has been shown to correlate with better prognosis and patient response to chemotherapy, some studies suggest that PIP may also play a role in metastasis. Here, we investigated the role of PIP in BC using the well-established 4T1 and E0771 mouse BC cell lines. Stable expression of PIP in both cell lines did not significantly alter their proliferation, migration, and response to anticancer drugs in vitro compared to empty vector control. To assess the effect of PIP expression on breast tumorigenesis in vivo, the 4T1 syngeneic transplantable mouse model was utilized. In immunocompetent syngeneic BALB/c mice, PIP-expressing 4T1 primary tumors displayed delayed tumor onset and reduced tumor growth, and this was associated with higher percentages of natural killer cells and reduced percentages of type 2 T-helper cells in the tumor environment. The delayed tumor onset and growth were abrogated in immunodeficient mice, suggesting that PIP-mediated modulation of primary tumor growth involves an intact immune system. Paradoxically, we also observed that PIP expression was associated with a higher number of 4T1 colonies in the lungs in both the immunocompetent and immunodeficient mice. Gene expression analysis of PIP-expressing 4T1 cells (4T1-PIP) revealed that genes associated with tumor metastasis such as CCL7, MMP3 and MMP13, were significantly upregulated in 4T1-PIP cells when compared to the empty vector control (4T1-EV) cells. Collectively, these studies strongly suggest that PIP may possess a double-edge sword effect in BC, enhancing both antitumor immunity as well as metastasis.
Modeling Postnatal Hearing Case Finding Within the Italian National Health System
Authors: Orzan Eva , Pizzamiglio Giulia , Marchi Raffaella , Muzzi Enrico , Monasta Lorenzo , Torelli Lucio , Feresin Agnese
Published: March 2021

Objective: Despite the successful implementation of newborn hearing screening (NHS), a debate is emerging as to what should be the best means of enabling timely diagnosis and intervention for preschoolers with educationally significant sensorineural or conductive hearing impairment (HI) missed at the time of NHS or occurred after birth. Our study aims to document the proportion and characteristics of HIs diagnosed in children in need of audiologic assessment, in order to outline the optimization areas of an operational framework for auditory surveillance during preschool age.

Method: The referral routes and outcomes of 730 audiological assessments performed in 3 years within the framework of the early hearing identification program in Trieste (Italy) were retrospectively analyzed.

Results: Among 570/595 completed evaluations, an HI was diagnosed in 114 children, 73.7% of which presenting an exclusively conductive HI due to middle ear effusion. HIs were found in 36/141 who failed NHS, and 60/385 preschoolers who were referred by the primary care pediatrician's surveillance activity during well-child visits, with diagnostic yield of 25.5 and 15.5%, respectively.

Conclusion: Ongoing preschool surveillance in primary care setting integrated into a NHS program is feasible to conduct and may effectively identify HIs that missed NHS or were related with a risk factor. New triage instruments and protocols for immediate audiology referral could allow to obtain the diagnosis of educationally significant conductive and sensorineural HIs ahead of the development concern and in the same way reduce patient mobility, thus optimizing timing efficiency and economic impact of the program.
Antimicrobial Activity of Necklace Orchids is Phylogenetically Clustered and can be Predicted With a Biological Response Method
Authors: Wati Richa Kusuma , de Graaf Esmée F. , Bogarín Diego , Heijungs Reinout , van Vugt Rogier , Smets Erik F. , Gravendeel Barbara
Published: March 2021

Necklace orchids (Coelogyninae, Epidendroideae) have been used in traditional medicine practices for centuries. Previous studies on a subset of unrelated orchid species utilized in these traditional practices revealed they possessed antimicrobial, anti-inflammatory, and anti-oxidant activity, providing experimental proof for their medicinal properties. To date however none of these species have been investigated ethno-botanically in a phylogenetic context. This study carried out comparative bioprospecting for a group of wild orchids using EBDCS (the Economic Botany Data Collection Standards) organ targeted and biological response methods. The traditional medicinal use of necklace orchids was recorded from books and journals published between 1984 and 2016. Two orchids,Coelogyne cristataandCoelogyne fimbriata, were selected, cultivated both indoors and outdoors, and the antimicrobial properties on extracts from their leaves and pseudobulbs tested against a selection of human pathogens. A molecular phylogeny of Coelogyninae based on nuclear ribosomal ITS and plastidmatKDNA sequences obtained from 148 species was reconstructed with Maximum Likelihood (ML) using RAxML, Maximum Parsimony (MP) using PAUP and Bayesian Inference using MrBayes. Bioprospecting comparison of EBDCS and biological response was carried out using customized R scripts. Ethanolic extracts obtained from leaves ofC. fimbriatainhibited growth ofBacillus cereus,Staphylococcus aureus, andYersinia enterocolitica,confirming the antimicrobial properties of these extracts. Leaf extracts were found to have slightly stronger antimicrobial properties for plants cultivated outdoors than indoors. These differences were not found to be statistically significant though. Three hot nodes with high potency for antimicrobial activities were detected with the EBDCS organ targeted classification method, and eight hot nodes were detected with the biological response classification method. The biological response classification method is thus a more effective tool in finding hot nodes amongst clades of species with high medicinal potential.
Life-Long Hyperbilirubinemia Exposure and Bilirubin Priming Prevent In Vitro Metabolic Damage
Authors: Bianco Annalisa , Pinci Serena , Tiribelli Claudio , Bellarosa Cristina
Published: March 2021

Background: Unconjugated bilirubin (UCB) is more than the final product of heme catabolism. Mildly elevated systemic bilirubin concentrations, such as in Gilbert syndrome (GS), protect against various oxidative stress-mediated and metabolic diseases, including cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome, cancer, and age-related disease. The Gunn rat is an animal model of hereditary hyperbilirubinemia widely used in assessing the effect of high serum bilirubin concentration in various organs. The present work aims to understand if life-long hyperbilirubinemia and bilirubin-priming might contribute to protection against atherosclerosis and diabetic nephropathy (DN) at the cellular level.

Methods: Primary aortic endothelial cells and podocytes obtained from hyperbilirubinemic homozygous jj and normobilirubinemic heterozygous Nj Gunn rats were exposed to Palmitic Acid (PA) and Angiotensin II (Ang II), respectively, and the effects on cell viability and the activation of damage-related metabolic pathways evaluated. Results were validated on immortalized H5V and HK2 cells exposed to damage after UCB pretreatment.

Results: In both primary cell models, cells obtained from jj Gunn rats showed as significantly higher than Nj Gunn rats at any dose of the toxic agent. Reduction in CHOP expression and IL-6 release was observed in jj primary aortic endothelial cells exposed to PA compared to Nj cells. The same occurred on H5V pretreated with Unconjugated bilirubin. Upon Ang II treatment, primary podocytes from jj Gunn rats showed lower DNA fragmentation, cleaved caspase-3, and cleaved PARP induction than primary podocytes from Nj Gunn rats. In HK2 cells, the induction by Ang II of HIF-1α and LOXl2 was significantly reduced by UCB pretreatment.

Conclusion: Our data suggest that in models of atherosclerosis and DN life–long hyperbilirubinemia exposure or bilirubin-priming significantly contribute to decrease the injury by enhancing thecellular defensive response,
Side by Side: Reflections on Two Lifetimes of Dance
Authors: Kipling Brown Ann , Penniston Gray Anne
Published: March 2021

Telling stories about our experiences in dance brings to light unconscious knowledge and memories of the past and helps us understand our own decisions and practices. Reflexivity and story telling is central in the process of remembering and embodies some of the key aspects of autoethnography as a research tool. We are directed to examine and reflect on our experiences, analyzing goals and intentions, making connections between happenings and recounting each single experience. Dance has the potential for positive impact on both physical and mental health among professional dancers as well as among dance students and has the power to connect them to culture and community in unique and important ways. Research has provided evidence that arts engagement provides positive forms of social inclusion, opportunities to share arts, culture, language, and values and points to the value of the arts in the prevention and amelioration of health problems. Together with those benefits of a dance experience there is clear evidence of what can be learned in, through and about dance. In this time of the Covid-19 pandemic it seemed more relevant and poignant to examine our own experiences in dance as well as those experiences of others that have influenced our lives.
All for One and One for All? – Examining Convergent Validity and Responsiveness of the German Versions of the Tinnitus Questionnaire (TQ), Tinnitus Handicap Inventory (THI), and Tinnitus Functional Index (TFI)
Authors: Boecking Benjamin , Brueggemann Petra , Kleinjung Tobias , Mazurek Birgit
Published: March 2021

Background

Measurement of tinnitus-related distress and treatment responsiveness is key in understanding, conceptualizing and addressing this often-disabling symptom. Whilst several self-report measures exist, the heterogeneity of patient populations, available translations, and treatment contexts requires ongoing psychometric replication and validation efforts.

Objective

To investigate the convergent validity and responsiveness of the German versions of the Tinnitus Questionnaire [TQ], Tinnitus Handicap Inventory [THI], and Tinnitus Functional Index [TFI] in a large German-speaking sample of patients with chronic tinnitus who completed a psychologically anchored 7-day Intensive Multimodal Treatment Programme.

Methods

Two-hundred-and-ten patients with chronic tinnitus completed all three questionnaires at baseline and post-treatment. Intraclass correlation coefficients determined the convergent validity of each questionnaire’s total and subscale scores. Treatment responsiveness was investigated by [a] comparing treatment-related change in responders vs. non-responders as classified by each questionnaire’s minimal clinically important difference-threshold, and [b] comparing agreement between the questionnaires’ responder classifications.

Results

The total scores of all three questionnaires showed high agreement before and after therapy (TQ | THI: 0.80 [Pre], 0.83 [Post], TQ | TFI: 0.72 [Pre], 0.78 [Post], THI | TFI: 0.76 [Pre] 0.80 [Post]). All total scores changed significantly with treatment yielding small effect sizes. The TQ and TFI yielded comparable (19.65 and 18.64%) and the THI higher responder rates (38.15%). The TQ | THI and TQ | TFI showed fair, and the THI | TFI moderate agreement of responder classifications. Independent of classification, responders showed significantly higher change rates than non-responders across most scores. Each questionnaire’s total change score distinguished between responders and non-responders as classified by the remaining two questionnaires.

Conclusion

The total scores of all three questionnaires show high convergent validity and thus, comparability across clinical and research contexts. By contrast, subscale scores show high inconsistency. Whilst the TFI appears well suited for research purposes, the THI may be better suited to measure psychological aspects of tinnitus-related distress and their changes with accordingly focused treatment approaches.
Case Report: Burden of Illness in Narcolepsy Type 1: Hikikomori in a Teenage Girl
Authors: Filardi Marco , Blunda Vincenza , Vandi Stefano , Musetti Alessandro , Posar Annio , Visconti Paola , Pizza Fabio , Plazzi Giuseppe , Franceschini Christian
Published: March 2021

Narcolepsy type 1 (NT1) deeply impacts on quality of life, especially during adolescence, with NT1 children and adolescents that frequently report difficulties in integration with peers and decreased participation in after-school activities. Here we describe the case of NT1 teenager girl presenting with severe physical and social withdrawal, fulfilling the proposed diagnostic criteria for hikikomori, together with the classic NT1 symptoms. Social withdrawal is an overlooked phenomenon among NT1 children and adolescents that, if present, require a multidisciplinary approach and personalized interventions, but patients can benefit from NT1 pharmacological treatment.
Psychological Impact of the COVID-19 Pandemic on Adults and Their Children in Italy
Authors: Davico Chiara , Ghiggia Ada , Marcotulli Daniele , Ricci Federica , Amianto Federico , Vitiello Benedetto
Published: March 2021

Aim: The coronavirus disease 2019 (COVID-19) pandemic has abruptly changed the life of millions as travel and social contacts have been severely restricted. We assessed the psychological impact of COVID-19 on adults and children, with special attention to health care workers (HCWs).

Methods: A self-rated online survey, including the Impact of Event Scale-Revised (IES-R) for adults and the Children Revised Impact of Event Scale-Revised-13 items (CRIES-13) for their 8–18-year-old offspring, was conducted in Italy on March 20–26, 2020. Linear mixed-effects models were applied to the data, accounting for age, sex, education, and other demographic characteristics.

Results: Data were available from 2,419 adults (78.4% females, mean age 38.1 ± SD 13.1 years; 15.7% HCW) and 786 children (50.1% male, mean age 12.3 ± 3.2 years). Median (IQR) IES-R score was 30.0 (21.0–40.0), corresponding to mild psychological impact, with 33.2% reporting severe psychological impact. IES-R was lower in HCWs (29.0) than non-HCWs (31.0), but HCWs directly involved in COVID-19 care had higher scores [33.0 (26.0–43.2)] than uninvolved HCWs [28.0 (19.0–36.0)]. Median CRIES-13 score was [21.0 (11.0–32.0)], with 30.9% of the children at high risk for post-traumatic stress disorder. Parent and child scores were correlated.

Conclusions: Up to 30% of adult and children in the pandemic area are at high risk for post-traumatic stress disturbances. The risk is greater for HCWs directly involved in COVID-19 care and for their children.
Borderline Personality Features in Patients With Persistent Depressive Disorder and Their Effect on CBASP Outcome
Authors: Konvalin Franziska , Grosse-Wentrup Fabienne , Nenov-Matt Tabea , Fischer Kai , Barton Barbara B. , Goerigk Stephan , Brakemeier Eva-Lotta , Musil Richard , Jobst Andrea , Padberg Frank , Reinhard Matthias A.
Published: March 2021

Introduction: The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) was developed for the treatment of persistent depressive disorder (PDD), where comorbid personality disorders (PD) are common. In contrast to other PD, comorbid borderline personality disorder (BPD) is often regarded as an exclusion criterion for CBASP. In clinical settings, however, subthreshold BPD symptoms are prevalent in PDD and may not be obvious at an initial assessment prior to therapy. As data on their impact on CBASP outcome are very limited, this naturalistic study investigates BPD features in PDD and their relevance for the therapeutic outcome of a multimodal CBASP inpatient program.

Method: Sixty patients (37 female, mean age 38.3, SD 11.9 years) meeting DSM-5 criteria for PDD underwent a 10 weeks CBASP inpatient program. BPD features (i.e., number of fulfilled DSM-5 criteria) together with childhood maltreatment and rejection sensitivity were assessed on admission. Before and after treatment, severity of depressive symptoms was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI-II). BPD symptoms were assessed using the Borderline Personality Disorder Severity Index (BPDSI-IV) and the Borderline Symptom List (BSL-23). Intercorrelations of baseline characteristics and symptom change during treatment were analyzed.

Results: Patients with PDD met a mean of 1.5 (SD 1.6) BPD criteria with 4 patients fulfilling ≥5 criteria. BPD symptoms and depressive symptoms showed a strong correlation, and BPD symptoms were additionally correlated with emotional abuse and rejection sensitivity. There was no association between BPD features at baseline and improvement on the MADRS, however, BPD features tended to be associated with a lower response according to the BDI-II score after 10 weeks of treatment. Furthermore, BPD symptoms (i.e., abandonment, impulsivity and affective instability) were reduced after 10 weeks of CBASP treatment.

Discussion: BPD symptoms are prevalent in patients with PDD and highly intertwined with the experience of depressive symptoms. In this naturalistic study in PDD, BPD features at baseline did not limit the clinical response to CBASP. Future studies may extend the spectrum of PDD to comorbid subsyndromal or even syndromal BPD in order to develop tailored psychotherapeutic treatment for these complex affective disorders.
Pandemic Uncertainty and Socially Responsible Investments
Authors: Zhu Wenzhong , Yang Jiajia , Lv Han , Zhuang Meier
Published: March 2021

This paper examines the effects of pandemic uncertainty on socially responsible investments. We use the overall corporate sustainability performance index in the Global-100 Most Sustainable Corporations in the World dataset to measure socially responsible investments. The global pandemic uncertainty is also measured by the World Pandemic Uncertainty Index. We focus on the panel dataset from 2012 to 2020, and the results show that the World Pandemic Uncertainty Index is positively related to socially responsible investments. The main findings remain significant when we utilize various panel estimation techniques.