Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell therapy to improve regeneration of skeletal muscle injuries

Diseases that jeopardize the musculoskeletal system and cause chronic impairment are prevalent throughout the Western world. In Germany alone, ~1.8 million patients suffer from these diseases annually, and medical expenses have been reported to reach 34.2bn Euros. Although musculoskeletal disorders are seldom fatal, they compromise quality of life and diminish functional capacity. For example, musculoskeletal disorders incur an annual loss of over 0.8 million workforce years to the German economy. Among these diseases, traumatic skeletal muscle injuries are especially problematic because they can occur owing to a variety of causes and are very challenging to treat. In contrast to chronic muscle diseases such as dystrophy, sarcopenia, or cachexia, traumatic muscle injuries inflict damage to localized muscle groups. Although minor muscle trauma heals without severe consequences, no reliable clinical strategy exists to prevent excessive fibrosis or fatty degeneration, both of which occur after severe traumatic injury and contribute to muscle degeneration and dysfunction. Of the many proposed strategies, cell‐based approaches have shown the most promising results in numerous pre‐clinical studies and have demonstrated success in the handful of clinical trials performed so far. A number of myogenic and non‐myogenic cell types benefit muscle healing, either by directly participating in new tissue formation or by stimulating the endogenous processes of muscle repair. These cell types operate via distinct modes of action, and they demonstrate varying levels of feasibility for muscle regeneration depending, to an extent, on the muscle injury model used. While in some models the injury naturally resolves over time, other models have been developed to recapitulate the peculiarities of real‐life injuries and therefore mimic the structural and functional impairment observed in humans. Existing limitations of cell therapy approaches include issues related to autologous harvesting, expansion and sorting protocols, optimal dosage, and viability after transplantation. Several clinical trials have been performed to treat skeletal muscle injuries using myogenic progenitor cells or multipotent stromal cells, with promising outcomes. Recent improvements in our understanding of cell behaviour and the mechanistic basis for their modes of action have led to a new paradigm in cell therapies where physical, chemical, and signalling cues presented through biomaterials can instruct cells and enhance their regenerative capacity. Altogether, these studies and experiences provide a positive outlook on future opportunities towards innovative cell‐based solutions for treating traumatic muscle injuries—a so far unmet clinical need.
Managing Pharmacotherapy in People Living With HIV and Concomitant Malignancy

Objective: To describe data with selected malignancies in people living with HIV (PLWH) and HIV in individuals affected by both conditions and to summarize drug-drug interactions (DDIs) with clinical recommendations for point-of-care review of combination therapies. Data Sources: Literature searches were performed (2005 to December 2018) in MEDLINE and EMBASE to identify studies of malignancies in PLWH in the modern era. Study Selection and Data Extraction: Article bibliographies and drug interaction databases were reviewed. Search terms included HIV, antiretroviral therapy, antineoplastic agents, malignancies, and drug interactions. Data Synthesis: In the pre–antiretroviral therapy (ART) era, malignancies in PLWH were AIDS-defining illnesses, and life expectancy was shorter. Nowadays, PLWH are living longer and developing malignancies, including lung, anal, and prostate cancers. Concurrently, the oncology landscape has evolved, with novel oral targeted agents and immunotherapies becoming routine elements of care. The increased need for and complexity with antineoplastics in PLWH has led to recommendations for multidisciplinary care of this unique population. Evaluation of DDIs requires review of metabolic pathways, absorption mechanisms, and various drug transporters associated with antineoplastics and ART. Relevance to Patient Care and Clinical Practice: This review summarizes available data of non–AIDS-defining malignancies, principles of HIV care in the patient with malignancy, and guidance for assessing DDIs between antineoplastics and ART. Summary DDI tables provide point-of-care recommendations. Conclusions: The availability of ART has transformed AIDS into a chronic medical condition, and PLWH are experiencing age-related malignancies. Pharmacists play an important role in the management of this patient population.
Comparing Mental Health across Distinct Groups of Users of Psychedelics, MDMA, Psychostimulants, and Cannabis

ABSTRACT Differences in mental health (MH) of users of distinct psychoactive substances have been shown. Both substance use (SU) and MH in users are influenced by stressful life events. This study compared MH parameters in distinct groups of substance users and evaluated the impact of stress factors on these outcomes. Data stem from the longitudinal Swiss Cohort Study on Substance Use Risk Factors (C-SURF) involving 4,475 young adult men. Distinct groups were created for the past 12 months’ use of psychedelics, MDMA, psychostimulants, and cannabis. MH measurements (depressive symptoms, overall MH, perceived stress, life satisfaction) were used as outcome variables, while indicators of past family functioning and stressful life events served as covariates. The MH of psychedelics users was not significantly different from the no-drug-use group, whereas poorer MH was found in the other SU groups. Observed effects were influenced by the tested stress factors. The absence of association between use of psychedelics and worsening of MH deserves further investigation in male and female samples. Stressful life experiences must be considered when assessing the MH of users of illicit substances. These findings suggest that some men practice SU as self-medication to cope with life adversity.
Human papillomavirus variants among Inuit women in northern Quebec, Canada

Background Inuit communities in northern Quebec have high rates of human papillomavirus (HPV) infection, cervical cancer and cervical cancer–related mortality as compared to the Canadian population. HPV types can be further classified as intratypic variants based on the extent of homology in their nucleotide sequences. There is limited information on the distribution of intratypic variants in circumpolar areas. Objective Our goal was to describe the HPV intratypic variants and associated baseline characteristics. Design We collected cervical cell samples in 2002–2006 from 676 Inuit women between the ages of 15 and 69 years in Nunavik. DNA isolates from high-risk HPVs were sequenced to determine the intratypic variant. Results There were 149 women that were positive for HPVs 16, 18, 31, 33, 35, 45, 52, 56 or 58 during follow-up. There were 5 different HPV16 variants, all of European lineage, among the 57 women positive for this type. There were 8 different variants of HPV18 present and all were of European lineage (n=21). The majority of samples of HPV31 (n=52) were of lineage B. The number of isolates and diversity of the other HPV types was low. Age was the only covariate associated with HPV16 variant category. Conclusions These frequencies are similar to what was seen in another circumpolar region of Canada, although there appears to be less diversity as only European variants were detected. This study shows that most variants were clustered in one lineage for each HPV type.
Maternal perinatal representations and their associations with mother-infant interaction and attachment: A longitudinal comparison of Portuguese and Brazilian dyads.

Prior research in Western countries (mostly the US, Canada and northern Europe) indicates that mothers' representations are associated with mother-infant interaction quality and their child's attachment security later in the first year. Fewer studies, however, have evaluated whether these associations hold for mother-infant dyads in other countries, such as Brazil and Portugal. Although these countries share a similar language and culture, they differ on societal dimensions that may affect parenting attitudes and mother-infant relationships, such as economic stress, social organisation, social policy, and the availability of services for young families. In this longitudinal study, we followed two independent samples of Brazilian and Portuguese mother-infant dyads from the perinatal period to 12 months post-partum. We assessed mothers' perinatal representations using semi-structured interviews in the first 48 hours after the infant's birth, and evaluated the associations of these representations with mother interaction quality at 9 months and infant attachment at 12 months. Results were similar in each country, corroborating prior research in single Western countries: Mothers with more positive perinatal representations were more sensitive to their infants during free play at 9 months and were more likely to have infants classified as securely attached at 12 months.
Suppression of connexin 43 expression by miR-106a promotes melanoma cell proliferation.

OBJECTIVE Connexin 43 (Cx43), a vital gap junction protein is reported to be involved in melanoma progression. The aim of the study is to investigate the regulatory role of Cx43 in melanoma. MATERIALS AND METHODS Western blot assay was used to detect the protein expression of Cx43 in melanoma cells and the human epidermal melanocytes (HEMn). MTT cell proliferation and cell colony formation assays were used to assess cell proliferation. Bioinformatics prediction, luciferase reporter assay, Western blot and qRT-PCR assays were applied to demonstrate that Cx43 was a direct target of miR-106a in melanoma cells. RESULTS Connexin 43 (Cx43) was lower expressed in melanoma cells compared with human epidermal melanocytes (HEMn). Cx43 overexpression significantly inhibited melanoma cell proliferation and colony formation ability in vitro. However, knockdown of Cx43 had opposite effects on cell proliferation and colony formation. Bioinformatics prediction and luciferase reporter assays demonstrated that miR-106a targeted the 3' untranslated region (3'UTR) of Cx43 and regulated its mRNA and protein expression levels in melanoma cells. MiR-106a was upregulated in melanoma cells, and its overexpression attenuated the effects caused by upregulating Cx43 expression. CONCLUSIONS Thus, our results indicated that Cx43 was downregulated in melanoma cells and may be a potential target of melanoma treatment.
Finding relevant documents using top ranking sentences: an evaluation of two alternative schemes

In this paper we present an evaluation of techniques that are designed to encourage web searchers to interact more with the results of a web search. Two specific techniques are examined: the presentation of sentences that highly match the searcher's query and the use of implicit evidence. Implicit evidence is evidence captured from the searcher's interaction with the retrieval results and is used to automatically update the display. Our evaluation concentrates on the effectiveness and subject perception of these techniques. The results show, with statistical significance, that the techniques are effective and efficient for information seeking.
Recovery of Oligomeric Proanthocyanidins and Other Phenolic Compounds with Established Bioactivity from Grape Seed By-Products

Grape seeds are a copious part of the grape pomace produced by wine and juice industry and they represent an interesting source of phenolic compounds. Proanthocyanidins (PAs) are the main class of grape seed phenols and are important dietary supplements for their well-known beneficial properties. In this study enriched extracts obtained from Chardonnay and Pignoletto grape seeds were characterized for their proanthocyanidins and other minor phenolic compounds content and composition. Seed PAs were fractionated using Sephadex LH-20, using different ethanol aqueous solutions as mobile phase and analysed by normal phase HPLC-FLD-ESI-MS. Monomers, oligomers up to dodecamers and polymers were recorded in all samples. For both cultivars, the extracts showed a high content in PAs. The determination of other phenolic compounds was carried out using a HPLC-QqQ-ESI-MS and Chardonnay samples reported a greater content compared to Pignoletto samples. Contrary to PAs fraction, extracts obtained with ethanol/water 50/50 (v/v) presented a significant higher phenolic content than the others.
Relationship between Circulating Serpina3g, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinase-1 and -2 with Chronic Obstructive Pulmonary Disease Severity

Chronic obstructive pulmonary disease (COPD) is influenced by genetic and environmental factors. A protease-antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. Here, we examined the relationship between circulating serpina3g, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 and -2 (TIMP-1 and -2, respectively) and severity of COPD. We included 150 stable COPD patients and 35 control subjects in the study. The COPD patients were classified into four groups (I, II, III, and IV), according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines based on the severity of symptoms and the exacerbation risk. Plasma serpina3g, MMP-9, and TIMP-1 and -2 concentrations were significantly higher in the all patients than in control subjects. Plasma serpina3g, MMP-9, and TIMP-1 and -2 concentrations were significantly higher in groups III and IV than in groups I and II. A negative correlation between serpina3g, MMP-9, and TIMP-1 and -2 levels and the forced expiratory volume in 1 s (FEV1) was observed. MMP-9 concentration and the MMP-9/TIMP-1 ratio were higher in patients with emphysema than in other phenotypes (both with p < 0.01). The findings of this study suggest that circulating serpina3g, MMP-9, and TIMP-1 and -2 levels may play an important role in airway remodeling in COPD pathogenesis. Disrupted protease-antiprotease imbalance in patients with COPD is related to the presence of airway injury. MMP-9 concentration and the MMP-9/TIMP-1 ratio are the best predictors of emphysema in COPD patients.
Current Status of p16 Immunohistochemistry and HPV Testing in Fine Needle Aspiration Specimens of the Head and Neck

Human papilloma virus (HPV)-related squamous cell carcinoma (SCC) is biologically unique and has a better prognosis than conventional SCC of the head and neck. p16 immunohistochemistry emerged as a valuable surrogate marker for HPV in oropharyngeal SCC. The criteria for a positive p16 result in tissue specimens are well established. However, there is no consensus regarding interpreting p16 staining in cell blocks and other cytology specimens. This review discusses the current evidence on p16 testing in cytology specimens and also highlights other methods for HPV testing, including DNA and RNA in situ hybridization, as well as other molecular HPV tests.
On the Design of BSB Neural Associative Memories Using Semidefinite Programming

This article is concerned with the reliable search for optimally performing BSB (brain state in a box) neural associative memories given a set of prototype patterns to be stored as stable equilibrium points. By converting and/or modifying the nonlinear constraints of a known formulation for the synthesis of BSB-based associative memories into linear matrix inequalities, we recast the synthesis into semidefinite programming problems and solve them by recently developed interior point methods. The validity of this approach is illustrated by a design example.
Partisan Bias and Its Discontents

Baron and Jost (this issue, p. 292) present three critiques of our meta-analysis demonstrating similar levels of partisan bias in liberals and conservatives: (a) that the studies we examined were biased toward finding symmetrical bias among liberals and conservatives, (b) that the studies we examined do not measure partisan bias but rather rational Bayesian updating, and (c) that social psychology is not biased in favor of liberals but rather toward creating false equivalencies. We respond in turn that (a) the included studies covered a wide variety of issues at the core of contemporary political conflict and fairly compared bias by establishing conditions under which both liberals and conservatives would have similar motivations and opportunities to demonstrate bias; (b) we carefully selected studies that were least vulnerable to Bayesian counterexplanation, and most scientists and laypeople consider these studies demonstrations of bias; and (c) there is reason to be vigilant about liberal bias in social psychology, but this does not preclude concerns about other possible biases, all of which threaten good science. We close with recommendations for future research and urge researchers to move beyond broad generalizations of political differences that are insensitive to time and context.
Emergence of analogy from relation learning

Significance The ability to learn and make inferences based on relations is central to intelligence, underlying the distinctively human ability to reason by analogy across dissimilar situations. We have developed a computational model demonstrating that abstract relations, such as synonymy and antonymy, can be learned efficiently from semantic feature vectors for individual words and can be used to solve simple verbal analogy problems with close to human-level accuracy. The approach illustrates the potential synergy between deep learning from “big data” and supervised learning from “small data. ” Core properties of high-level intelligence can emerge from relatively simple computations coupled with rich semantics. The model illustrates how operations on nonrelational inputs can give rise to protosymbolic relational representations. By middle childhood, humans are able to learn abstract semantic relations (e.g., antonym, synonym, category membership) and use them to reason by analogy. A deep theoretical challenge is to show how such abstract relations can arise from nonrelational inputs, thereby providing key elements of a protosymbolic representation system. We have developed a computational model that exploits the potential synergy between deep learning from “big data” (to create semantic features for individual words) and supervised learning from “small data” (to create representations of semantic relations between words). Given as inputs labeled pairs of lexical representations extracted by deep learning, the model creates augmented representations by remapping features according to the rank of differences between values for the two words in each pair. These augmented representations aid in coping with the feature alignment problem (e.g., matching those features that make “love-hate” an antonym with the different features that make “rich-poor” an antonym). The model extracts weight distributions that are used to estimate the probabilities that new word pairs instantiate each relation, capturing the pattern of human typicality judgments for a broad range of abstract semantic relations. A measure of relational similarity can be derived and used to solve simple verbal analogies with human-level accuracy. Because each acquired relation has a modular representation, basic symbolic operations are enabled (notably, the converse of any learned relation can be formed without additional training). Abstract semantic relations can be induced by bootstrapping from nonrelational inputs, thereby enabling relational generalization and analogical reasoning.
Pathophysiology and management of opioid-induced constipation: European expert consensus statement

Background Opioid-induced bowel dysfunction is a complication of opioid therapy, in which constipation is the most common and problematic symptom. However, it is frequently under-recognised and thus effective management is often not instituted despite a number of treatment options. Objective The central objective of this study is to provide a summary of the pathophysiology and clinical evaluation of opioid-induced constipation and to provide a pragmatic management algorithm for day-to-day clinical practice. Methods This summary and the treatment algorithm is based on the opinion of a European expert panel evaluating current evidence in the literature. Results The pathophysiology of opioid-induced constipation is multi-faceted. The key aspect of managing opioid-induced constipation is early recognition. Specific management includes increasing fluid intake, exercise and standard laxatives as well as addressing exacerbating factors. The Bowel Function Index is a useful way of objectively evaluating severity of opioid-induced constipation and monitoring response. Second-line treatments can be considered in those with recalcitrant symptoms, which include gut-restricted or peripherally acting mu-opioid receptor antagonists. However, a combination of interventions may be needed. Conclusion Opioid-induced constipation is a common, yet under-recognised and undertreated, complication of opioid therapy. We provide a pragmatic step-wise approach to opioid-induced constipation, which should simplify management for clinicians.
The Epidemiology of Breast Implant–Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand Confirms the Highest Risk for Grade 4 Surface Breast Implants

Background: The epidemiology and implant-specific risk for breast implant–associated (BIA) anaplastic large cell lymphoma (ALCL) has been previously reported for Australia and New Zealand. The authors now present updated data and risk assessment since their last report. Methods: New cases in Australia and New Zealand were identified and analyzed. Updated sales data from three leading breast implant manufacturers (i.e., Mentor, Allergan, and Silimed) were secured to estimate implant-specific risk. Results: A total of 26 new cases of BIA-ALCL were diagnosed between January of 2017 and April of 2018, increasing the total number of confirmed cases in Australia and New Zealand to 81. This represents a 47 percent increase in the number of reported cases over this period. The mean age and time to development remain unchanged. The implant-specific risk has increased for Silimed polyurethane (23.4 times higher) compared with Biocell, which has remained relatively static (16.5 times higher) compared with Siltex implants. Conclusions: The number of confirmed cases of BIA-ALCL in Australia and New Zealand continues to rise. The implant-specific risk has now changed to reflect a strong link to implant surface area/roughness as a major association with this cancer.