Miracle-dz/UniFAR-FTUs huggingface dataset:
Covid‐19 vaccination in patients with multiple myeloma: Focus on immune response

First Department of Medicine, Clinic Ottakring, Wilhelminen Cancer Research Institute, Vienna, Austria CIMA, IDISNA, CIBERONC, Clínica Universidad de Navarra, Pamplona, Spain Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA Erasmus MC Cancer Institute, Erasmus University of Rotterdam, Rotterdam, The Netherlands IBSAL, Cancer Research Center, University Hospital of Salamanca, Salamanca, Spain Department of Hematology, University Hospital Nantes, Nantes, France Hematology & Medical Oncology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
Assisting People With Their Living, Not Their Dying: Health Professionals’ Perspectives of Palliative Care and Opioids in ILD

Objectives: Interstitial lung disease (ILD) is a debilitating and life-limiting condition, requiring multi-disciplinary care. While guidelines recommend early specialist palliative care referral to improve symptoms and quality of life, few patients access such care towards the end-of-life. This study aimed to explore clinicians’ perspectives regarding specialist palliative care and opioids to understand barriers to optimal care and guide clinical practice improvement initiatives. Methods: A cross-sectional, exploratory, qualitative study was undertaken with Australian respiratory clinicians caring for people with ILD (n = 17). In-depth, semi-structured interviews were audio-recorded, transcribed verbatim and coded. Thematic analysis was undertaken to extrapolate recurring ideas from the data. Results: Four themes were identified: 1) understanding how to improve patient care and support, 2) the need to dispel stigmatized beliefs and misconceptions, 3) the importance of trusted relationships and good communication and 4) the challenges of navigating the health-care system. Participants discussed the need to implement early specialist palliative care and symptom palliation to alleviate symptoms, provide emotional support and augment quality of life. Participants described challenges accessing palliative care and opioids due to stigmatized beliefs amongst patients and clinicians and difficulties navigating the health-care system. Trusted therapeutic relationships with patients and strong inter-disciplinary partnerships with collaborative education and communication were perceived to improve patients’ access to symptom palliation. Conclusion: Specialist palliative care and opioids were believed to improve patients’ quality of life, however, many barriers can make accessing such care challenging. To address these issues, multi-disciplinary collaboration, high-quality communication and trusted therapeutic relationships are crucial throughout the ILD illness journey.
Benson's Disease or Posterior Cortical Atrophy, Revisited.

BACKGROUND D. Frank Benson and colleagues first described the clinical and neuropathological features of posterior cortical atrophy (PCA) from patients in the UCLA Neurobehavior Program. OBJECTIVE We reviewed the Program's subsequent clinical experience with PCA, and its potential for clarifying this relatively rare syndrome in comparison to the accumulated literature on PCA. METHODS Using the original criteria derived from this clinic, 65 patients with neuroimaging-supported PCA were diagnosed between 1995 and 2020. RESULTS On presentation, most have visual localization complaints and related visuospatial symptoms, but nearly half had memory complaints followed by symptoms of depression. Neurobehavioral testing showed predominant difficulty with visuospatial constructions, Gerstmann's syndrome, and Balint's syndrome, but also impaired memory and naming. On retrospective application of the current Consensus Criteria for PCA, 59 (91%) met PCA criteria with a modification allowing for "significantly greater visuospatial over memory and naming deficits. " There were 37 deaths (56.9%) with the median overall survival of 10.3 years (95% CI: 9.6-13.6 years), consistent with a slow neurodegenerative disorder in most patients. CONCLUSION Together, these findings recommend modifying the PCA criteria for "relatively spared" memory, language, and behavior to include secondary memory and naming difficulty and depression, with increased emphasis on the presence of Gerstmann's and Balint's syndromes.
Who Is Talking About Adverse Childhood Experiences? Evidence From Twitter to Inform Health Promotion

Background Growing availability of research about addressing adverse childhood experiences (ACEs) has recently been embraced by the mainstream media and public. Social media, especially Twitter, provides a unique forum and platform for the public to access and share information about this topic. Objective This study aims to better understand how the public is framing, sharing, and using research about ACEs on Twitter and to examine the information being commonly discussed about ACEs. Method We obtained tweets on the topics of ACEs, childhood resilience, and childhood trauma between January 1, 2018, and December 31, 2019. This timeframe was determined based on key related events in the mainstream media. Crimson Hexagon, a social media analytics system using Boolean logic, was used to identify salient topics, influencers, and conduct a content analysis. Results A total of 195,816 relevant tweets were obtained from our search. The weekly volume was approximately 1,864 tweets. Key topics included general use of the term ACEs (23%), trauma and ACEs (19%), long-term impact of ACEs (12%), preventing ACEs (11%), short-term effects of ACEs (8%), the 1997 ACE Study (5%), and students with ACEs (5%). The top two sentiments were fear and joy. Top conversation influencers included pediatricians, child health advocacy organizations, California’s state government, the Centers for Disease Control and Prevention, and National Public Radio. Conclusion This analysis provides insight to the ways the public is conversing about ACEs and related topics. Results indicated that conversations focus on increasing awareness of ACEs by content experts and public health organizations. This presents an opportunity to leverage social media tools to increase public engagement and awareness.
Changes in Grauer's gorilla (Gorilla beringei graueri) and other primate populations in the Kahuzi‐Biega National Park and Oku Community Reserve, the heart of Grauer's gorilla global range

Grauer's gorillas (Gorilla beringei graueri) have declined drastically across their range in eastern Democratic Republic of Congo (DRC). Survey data analysed in 2016 estimated a 77% decline in numbers between the mid‐ 1990s and 2016 and predicted that Kahuzi‐Biega National Park (KBNP), and the contiguous Oku Community Reserve (OCR) held much of the global population. An estimate of 3800 Grauer's gorillas was made across its range at that time. Here, we publish the most extensive survey of Grauer's gorilla numbers to date, using nest counts from 230 line transects across KBNP and OCR to derive more accurate estimates of both gorilla and chimpanzee numbers. Gorilla numbers were estimated from line transects at 1,571 (95% confidence interval [CI]: 824–2,993) within KBNP and at 2,244 (95% CI: 1,471–3,422) in OCR. Eastern chimpanzee (Pan troglodytes schweinfurthii) numbers were estimated at 2,500 (95% CI: 1,804–3,462) in KBNP and 687 (95% CI: 472–999) in OCR. Estimates of total numbers for the survey area were 5,252 (95% CI: 3,687–7,481) Grauer's gorillas and 4,275 (95% CI: 3,322–5,502) eastern chimpanzees. Chimpanzee numbers were not significantly different from the estimates in the mid‐1990s but the gorillas had significantly declined, mostly in KBNP. Modeled densities of these apes indicated that distances to mines, villages, or roads significantly explained part of the distribution of these apes, with higher densities also found in more rugged and remote sites. Other primates have all declined in this region, likely due to bushmeat hunting, especially the Endangered Ulindi River Red Colobus Piliocolobus lulindicus. These results confirm the negative impact of insecurity on Grauer's gorilla but indicate that the population declines may not be as great as previously feared. Using our revised gorilla density estimate we revise the original estimate of global numbers from 3,800 to 6,800 individuals.
Interdisciplinary Explorations: Promoting Critical Thinking via Problem-Based Learning in an Advanced Biochemistry Class

Interdisciplinary approaches to research in the sciences have become increasingly important in solving a wide range of pressing problems at both global and local levels. It is imperative then that science majors in higher education understand the need for exploring information from a wide array of disciplines. With this in mind, interdisciplinary instruction has the potential to bring new insights and methods to enhance learning and promote critical thinking skills while itself modeling the benefits of interdisciplinary practice in research. This paper explores an interdisciplinary collaboration between a librarian and a chemist seeking to improve student research and critical thinking skills through the utilization of problem-based learning. A module exploring the interdisciplinary nature of science was implemented for an advanced Biochemistry class and delivered in a library setting. Initial findings of this pilot project suggest that the implementation of a carefully constructed, problem-based curricul.
The Causes of Death and Pathological Findings of Kratom Users

Abstract Kratom is a psychoactive substance in Thailand. The major psychoactive chemical component of Kratom is mitragynine. This study aims to elucidate the characteristics and pathologies of autopsied cases where mitragynine was present and quantify the amounts of mitragynine. The autopsy reports in which the blood samples were positive for mitragynine were selected in Ramathibodi Hospital between January 2015 and December 2019. Data from autopsy reports comprised sex, age, circumstances of death, pathological findings, other substances, causes of death, and mitragynine concentrations. Mitragynine was quantitatively analyzed using liquid chromatography-mass spectrometry/mass spectrometry. Twenty-four cases from 2160 autopsy cases were found to be positive for mitragynine. The most commonly observed pathological findings were pulmonary edema (7 cases) and coronary atherosclerosis (6 cases). Antihistamine (8 cases), ethanol (4 cases), and amphetamine (4 cases) were commonly found. The mitragynine concentrations were 0.0035 to 3.6 mg/L (median 0.069). One interesting case involved a 43-year-old man whose pathological findings showed chronic asthma with a high concentration of mitragynine in the blood (3.6 mg/L), although no other substances were detected. In conclusion, the use of mitragynine may be a direct or indirect cause of death, whereas the lethal concentration has yet to be clearly determined.
Binding objects to their spatiotemporal context: Age gradient and neuropsychological correlates of What-Where-When task performance

Abstract A number of recent studies have shown that the ability to accurately recall bound object and spatiotemporal aspects of an experienced event develops gradually in children and is greatly impaired in the elderly, reflecting developmental discontinuities in the integrity of the underlying medial temporal lobe network. Using a novel What-Where-When (WWW) visuospatial reconstruction task, the experiential memory performance of a group of healthy older adults (aged 60–80) was compared to that of a group of younger adults (aged 20–40). Both groups were equated on their general cognitive ability, their executive functioning, and on the presence of depression, anxiety, and stress symptomatology. As hypothesized, the performance of the older adults in the binding task was significantly lower, with younger participants recalling three times the amount of bound object and spatiotemporal triads than their older counterparts. Psychomotor speed was found to be lower in older adults and was the only neuropsychological index to significantly affect success on the WWW binding task. Based on this and other relevant studies, the selective associative memory impairment obtained using a non-verbal What-Where-When paradigm emerges as a marker for the detection of early pre-clinical signs of experiential memory pathology.
Interrelationship between miRNA and splicing factors in pancreatic ductal adenocarcinoma

ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of diagnosis at late stage and inherent/acquired chemoresistance. Recent advances in genomic profiling and biology of this disease have not yet been translated to a relevant improvement in terms of disease management and patient’s survival. However, new possibilities for treatment may emerge from studies on key epigenetic factors. Deregulation of microRNA (miRNA) dependent gene expression and mRNA splicing are epigenetic processes that modulate the protein repertoire at the transcriptional level. These processes affect all aspects of PDAC pathogenesis and have great potential to unravel new therapeutic targets and/or biomarkers. Remarkably, several studies showed that they actually interact with each other in influencing PDAC progression. Some splicing factors directly interact with specific miRNAs and either facilitate or inhibit their expression, such as Rbfox2, which cleaves the well-known oncogenic miRNA miR-21. Conversely, miR-15a-5p and miR-25-3p significantly downregulate the splicing factor hnRNPA1 which acts also as a tumour suppressor gene and is involved in processing of miR-18a, which in turn, is a negative regulator of KRAS expression. Therefore, this review describes the interaction between splicing and miRNA, as well as bioinformatic tools to explore the effect of splicing modulation towards miRNA profiles, in order to exploit this interplay for the development of innovative treatments. Targeting aberrant splicing and deregulated miRNA, alone or in combination, may hopefully provide novel therapeutic approaches to fight the complex biology and the common treatment recalcitrance of PDAC.
Riedel's thyroiditis - difficulties in differentiating from thyroid cancer.

A hard, palpable mass localized in the perithyroidal soft tissue is often suposed of having a cancerous process. Along with dysphagia or neck pain, it causes patient and physician concern. It is important for a correct diagnosis to differentiate the disease with another with an identical clinical manifestation - a Riedel's thyroiditis. In Riedel's thyroiditis fibrosclerotic organ manifestations can either be a part of IgG4-related disease or solely be located in the thyroid and adjacent tissues and elevation of serum IgG4 can be found.
Adults with unilateral congenital ear canal atresia – sound localization ability and recognition of speech in competing speech in unaided condition

Abstract Background Individuals with unilateral hearing loss show poor spatial hearing, but individual variability is high. Aims/objectives To investigate if the degree of hearing loss in unilateral ear canal atresia affects horizontal sound localization and speech recognition. Materials and methods Twelve subjects with unilateral ear canal atresia without childhood hearing intervention. Previously published data from eight normal-hearing subjects in normal binaural as well as experimentally induced unilateral hearing loss served as a reference. Horizontal sound localization and recognition of speech in spatially separate competing speech were assessed. Results Linear regression analysis demonstrated a relationship between sound localization accuracy (SLA) and the air conduction pure tone average of the atretic ear (r = 0.85, p=.007). The large proportion of variability in SLA (72%) explained by the degree of hearing loss of the atretic ear indicates that binaural processing is possible. SLA was worse than for normal hearing individuals (p<.0001), and comparable to moderate simulated unilateral hearing loss (p=.13). Speech discrimination was significantly worse than normal (p<.0001) and not dependent on degree of hearing loss of the atretic ear. Conclusions and significance Individuals with congenital unilateral ear canal atresia show impaired horizontal SLA and recognition of speech in competing speech.
Interspecific competition and their impacts on the growth of macrophytes and pollutants removal within constructed wetland microcosms treating domestic wastewater

Abstract Eight free water surface constructed wetland microcosm (CWM) units are designed with single as well as mixed planting of Pistia stratiotes, Phragmites karka, and Typha latifolia with control to assess their competitive value (CV), relative growth rates (RGR), and pollutants removal efficiency. Further, the total dry biomass production and other growth parameters such as number of macrophytes, above-ground biomass, below-ground biomass, and root length were also measured to understand the dominant characteristics of the macrophytes. The CWM units with species mixture out-performed species monocultures. Removal of BOD, TP, SRP, NH4 +-N, NO3 −-N, and NO2 −-N by mixed planting of P. stratiotes and P. karka was higher at most of the time. Typha latifolia was the superior competitor against both P. stratiotes and P. karka due to its aggressive characteristics that inhibits the growth of neighboring macrophytes. However, P. karka was the superior competitor against P. stratiotes. The RGR of T. latifolia in all experimental units was almost two times more than that of P. karka. Novelty Statement The CWM units with species mixture out-performed species monocultures. CWMs with more than one macrophytic species are less vulnerable to seasonal fluctuations and more effective in contaminants removal as compared to single macrophyte wetlands. Removal of BOD, TP, SRP, NH4 +-N, NO3 −-N, and NO2 −-N by mixed planting of P. stratiotes and P. karka was higher at most of the time. The CWMs with P. stratiotes and P. karka are superior choice due to their higher wastewater nutrients removal capacity. The application of these three macrophytes in mixed cultures in free water surface constructed wetland is rare. The results are useful in designing large-scale multi-species wetlands which are less susceptible to seasonal variation and more effective in pollutants removal than single-species wetlands.
Stable overexpression of mutated PTEN in Chinese hamster ovary cells enhances their performance and therapeutic antibody production

Chinese hamster ovary (CHO) cells with a high viable cell density (VCD), resilience to culture stress, and the capacity to continuously express recombinant proteins are highly desirable. Phosphatase and tension homology deleted on chromosome ten (PTEN) functions as a key negative regulator of the PI3K/Akt signaling pathway, mediating cell growth and survival. Its oncogenic mutant endows cells with an enhanced proliferation rate and resistance to death. In this study, the role of oncogenic PTEN C124S or G129E on the performance of CHO‐K1 and CHO‐IgG cells was investigated. Our results showed that CHO‐K1 cells stably expressing PTEN C124S or G129E exhibited enhanced proliferation, reduced apoptosis rate, and increased transient expression of therapeutic antibodies compared to the control cells. Moreover, the stable overexpression of PTEN C124S or G129E endowed CHO‐IgG cells with higher cell viability, VCD, and antibody titers (yield increased by approximately 0.77‐fold) in the fed‐batch culture process and enhanced their performance in response to the addition of sodium lactate. Moreover, the engineering of mutated PTEN in CHO‐IgG cells did not alter antibody quality. Collectively, our data suggest that mutated PTEN is a potential target for improving the manufacture of therapeutic antibodies.
Autophagy and ALS: mechanistic insights and therapeutic implications

ABSTRACT Mechanisms of protein homeostasis are crucial for overseeing the clearance of misfolded and toxic proteins over the lifetime of an organism, thereby ensuring the health of neurons and other cells of the central nervous system. The highly conserved pathway of autophagy is particularly necessary for preventing and counteracting pathogenic insults that may lead to neurodegeneration. In line with this, mutations in genes that encode essential autophagy factors result in impaired autophagy and lead to neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS). However, the mechanistic details underlying the neuroprotective role of autophagy, neuronal resistance to autophagy induction, and the neuron-specific effects of autophagy-impairing mutations remain incompletely defined. Further, the manner and extent to which non-cell autonomous effects of autophagy dysfunction contribute to ALS pathogenesis are not fully understood. Here, we review the current understanding of the interplay between autophagy and ALS pathogenesis by providing an overview of critical steps in the autophagy pathway, with special focus on pivotal factors impaired by ALS-causing mutations, their physiologic effects on autophagy in disease models, and the cell type-specific mechanisms regulating autophagy in non-neuronal cells which, when impaired, can contribute to neurodegeneration. This review thereby provides a framework not only to guide further investigations of neuronal autophagy but also to refine therapeutic strategies for ALS and related neurodegenerative diseases. Abbreviations: ALS: amyotrophic lateral sclerosis; Atg: autophagy-related; CHMP2B: charged multivesicular body protein 2B; DPR: dipeptide repeat; FTD: frontotemporal dementia; iPSC: induced pluripotent stem cell; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PINK1: PTEN induced kinase 1; RNP: ribonuclear protein; sALS: sporadic ALS; SPHK1: sphingosine kinase 1; TARDBP/TDP-43: TAR DNA binding protein; TBK1: TANK-binding kinase 1; TFEB: transcription factor EB; ULK: unc-51 like autophagy activating kinase; UPR: unfolded protein response; UPS: ubiquitin-proteasome system; VCP: valosin containing protein.
Lung Function Impairment and the Risk of Incident Dementia: The Rotterdam Study

Background: The etiology of dementia may partly be underpinned by impaired lung function via systemic inflammation and hypoxia. Objective: To prospectively examine the association between chronic obstructive pulmonary disease (COPD) and subclinical impairments in lung function and the risk of dementia. Methods: In the Rotterdam Study, we assessed the risk of incident dementia in participants with Preserved Ratio Impaired Spirometry (PRISm; FEV1/FVC≥0.7, FEV1 < 80% predicted) and in participants with COPD (FEV1/FVC < 0.7) compared to those with normal spirometry (controls; FEV1/FVC≥0.7, FEV1≥80% predicted). Hazard ratios (HRs) with 95% confidence intervals (CI) for dementia were adjusted for age, sex, education attainment, smoking status, systolic blood pressure, body mass index, triglycerides, comorbidities and Apolipoprotein E (APOE) genotype. Results: Of 4,765 participants, 110 (2.3%) developed dementia after 3.3 years. Compared to controls, participants with PRISm, but not COPD, had an increased risk for all-type dementia (adjusted HRPRISm 2.70; 95% CI, 1.53–4.75; adjusted HRCOPD 1.03; 95% CI, 0.61–1.74). These findings were primarily driven by men and smokers. Similarly, participants with FVC% predicted values in the lowest quartile compared to those in the highest quartile were at increased risk of all-type dementia (adjusted HR 2.28; 95% CI, 1.31–3.98), as well as Alzheimer’s disease (AD; adjusted HR 2.13; 95% CI, 1.13–4.02). Conclusion: Participants with PRISm or a low FVC% predicted lung function were at increased risk of dementia, compared to those with normal spirometry or a higher FVC% predicted, respectively. Further research is needed to elucidate whether this association is causal and how PRISm might contribute to dementia pathogenesis.