Miracle-dz/UniFAR-FTUs huggingface dataset:
The side effect profile of Clozapine in real world data of three large mental health hospitals

Objective Mining the data contained within Electronic Health Records (EHRs) can potentially generate a greater understanding of medication effects in the real world, complementing what we know from Randomised control trials (RCTs). We Propose a text mining approach to detect adverse events and medication episodes from the clinical text to enhance our understanding of adverse effects related to Clozapine, the most effective antipsychotic drug for the management of treatment-resistant schizophrenia, but underutilised due to concerns over its side effects. Material and methods We used data from de-identified EHRs of three mental health trusts in the UK (>50 million documents, over 500,000 patients, 2835 of which were prescribed Clozapine). We explored the prevalence of 33 adverse effects by age, gender, ethnicity, smoking status and admission type three months before and after the patients started Clozapine treatment. Where possible, we compared the prevalence of adverse effects with those reported in the Side Effects Resource (SIDER). Results Sedation, fatigue, agitation, dizziness, hypersalivation, weight gain, tachycardia, headache, constipation and confusion were amongst the highest recorded Clozapine adverse effect in the three months following the start of treatment. Higher percentages of all adverse effects were found in the first month of Clozapine therapy. Using a significance level of (p< 0.05) our chi-square tests show a significant association between most of the ADRs and smoking status and hospital admission, and some in gender, ethnicity and age groups in all trusts hospitals. Later we combined the data from the three trusts hospitals to estimate the average effect of ADRs in each monthly interval. In gender and ethnicity, the results show significant association in 7 out of 33 ADRs, smoking status shows significant association in 21 out of 33 ADRs and hospital admission shows the significant association in 30 out of 33 ADRs. Conclusion A better understanding of how drugs work in the real world can complement clinical trials.
Towards a Greater Diversity of Replication Studies

: The replication of existing knowledge (e.g., previous study results) stands as an essential research practice across all science disciplines. Despite the importance of replication, the scarcity of replication studies is commonly criticized in business, management, and information system (IS) research. Therefore, efforts have already been made to facilitate replication research in the IS community, such as establishing conference tracks and journals focusing on publishing replication studies and providing guidelines on how and why to conduct replication research. Nonetheless, the perception of replication research remains unchanged, describing it as mundane. Therefore, in this issues and opinions article, we will explore how replication research could be made more appealing by diversifying the categories of replication studies. In this regard, we looked at replication in neuroscience, eliciting two new replication study categories: ‘transfer’ and ‘method. ’ Additionally, through extensive discussion with other IS scholars, we added one more replication category, ‘comparison. ’ We hope that this diversification will attract more researchers and also show the potential replication research holds.
Impact of Catastrophizing in Patients with Temporomandibular Disorders-A Systematic Review.

AIMS To assess the prevalence of catastrophizing in patients with temporomandibular disorders (TMD) and the possible associations between catastrophizing and treatment outcome. METHODS This review was registered in the Prospero database (CRD42018114233). Electronic searches were performed in PubMed, Scopus, and PsycINFO from the inception of each database up to October 26, 2018, and were combined with a hand search. Articles focusing on levels of catastrophizing and how catastrophizing affects pain levels and treatment outcomes for patients diagnosed with TMD were included, as well as studies reporting how treatment outcomes were affected by cognitive behavioral treatment as an addition to standard treatment for TMD. Reviews and case reports were excluded. Risk of bias was assessed with the Newcastle-Ottawa scale. RESULTS The literature search identified 266 articles. After screening of abstracts, the full texts of 59 articles were assessed. Of these, 37 articles, including 4,789 patients with TMD and 6,617 controls, met the inclusion criteria. Higher levels of pain catastrophizing were reported in patients with TMD, with a large effect size (Hedges' g = 0.86) compared to pain-free controls. Furthermore, associations of higher levels of catastrophizing with higher symptom severity and with poorer treatment outcome were reported together with indications of positive effects from cognitive behavioral therapy. CONCLUSION The results suggest an association between catastrophizing and TMD that may affect not only symptom severity but also treatment outcome. Assessing levels of pain catastrophizing might therefore be valuable in the assessment and management of patients with TMD.
Joint Assessment of Equilibrium and Neuromotor Function: A Validation Study in Patients with Fibromyalgia

Objective: To develop and validate a tool for evaluating balance and neuromotor function in patients with fibromyalgia (FMS). Methods: Brainstorming, the nominal group technique, and pilot-testing were used to select a battery of 20 functional balance tests that were included in a screening tool. A total of 108 subjects (62 with fibromyalgia syndrome, 22 aged over 65 years, and 24 healthy subjects) participated in this validation study. Factor validity, internal consistency, the ability to discriminate between patients and healthy subjects, and concurrent validity with the Fibromyalgia Impact Questionnaire (FIQ), the Central Sensitization Inventory (CSI), the 12-Item Short-Form Health Survey (SF-12), and other tools for measuring balance, such as the Dizziness Handicap Inventory (DHI), the Activities-Specific Balance Confidence Scale (ABC-16), the Falls Efficacy Scale-International (FES-I), and posturographic parameters, were evaluated. Results: The factorial analysis extracted four factors that explained 70% of the variance. The Alpha Cronbach value was 0.928. Concurrent validity of the screening tool with respect to other tools was high, and the receiver operating characteristic (ROC) curve analysis showed an AUC value of 0.932 for discriminating between healthy and FMS subjects. Severe balance disorder related to head movements in FMS patients was found. Conclusion: The 20-item JAEN (Joint Assessment of Equilibrium and Neuro-motor Function) screening tool is a valid and reliable tool for assessing balance in patients with FMS.
Risk factors for tumor recurrence in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma after esophagectomy

Objective To analyze the factors contributing to recurrence in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma (ESCC). Methods Patients with pT3N0M0 thoracic ESCC who underwent esophagectomy from January 2008 to December 2012 were included retrospectively. The last date of follow-up was 1 December 2016. Multivariate proportional hazard Cox models were used to identify factors associated with total (i.e., any) recurrence (TR), locoregional recurrence (LR), and distant metastasis (DM). Results A total of 692 patients were included. The median follow-up was 53 months (range: 3–107). The 3- and 5-year TR, LR, and DM rates were 35.8% and 41.0%, 28.7% and 32.1%, and 16.8% and 21.1%, respectively. The Cox analyses showed that the tumor location, number of dissected lymph nodes, and postoperative therapies were significantly associated with LR. The subgroup analysis showed that postoperative therapies could significantly decrease LR in the mediastinum but not in the neck and upper abdomen regions. Conclusions The recurrence rate of pT3N0M0 thoracic ESCC patients was high, especially for LR in the mediastinum. Postoperative therapies can significantly reduce the incidence of mediastinal recurrence.
Phenotypes, Developmental Basis, and Genetics of Pierre Robin Complex

The phenotype currently accepted as Pierre Robin syndrome/sequence/anomalad/complex (PR) is characterized by mandibular dysmorphology, glossoptosis, respiratory obstruction, and in some cases, cleft palate. A causative sequence of developmental events is hypothesized for PR, but few clear causal relationships between discovered genetic variants, dysregulated gene expression, precise cellular processes, pathogenesis, and PR-associated anomalies are documented. This review presents the current understanding of PR phenotypes, the proposed pathogenetic processes underlying them, select genes associated with PR, and available animal models that could be used to better understand the genetic basis and phenotypic variation of PR.
Eosinopenia in COVID-19 Patients: A Retrospective Analysis

Objectives: The aim of this study was to assess the diagnostic role of eosinophils count in COVID-19 patients. Methods: Retrospective analysis of patients admitted to our hospital with suspicion of COVID-19. Demographic, clinical and laboratory data were collected on admission. Eosinopenia was defined as eosinophils < 100 cells/mm3. The outcomes of this study were the association between eosinophils count on admission and positive real-time reverse transcription polymerase chain reaction (rRT-PCR) test and with suggestive chest computerized tomography (CT) of COVID-19 pneumonia. Results: A total of 174 patients was studied. Of those, 54% had positive rRT-PCR for SARS-CoV-2. A chest CT-scan was performed in 145 patients; 71% showed suggestive findings of COVID-19. Eosinophils on admission had a high predictive accuracy for positive rRT-PCR and suggestive chest CT-scan (area under the receiver operating characteristic—ROC curve, 0.84 (95% CIs 0.78–0.90) and 0.84 (95% CIs 0.77–0.91), respectively). Eosinopenia and high LDH were independent predictors of positive rRT-PCR, whereas eosinopenia, high body mass index and hypertension were predictors for suggestive CT-scan findings. Conclusions: Eosinopenia on admission could predict positive rRT-PCR test or suggestive chest CT-scan for COVID-19. This laboratory finding could help to identify patients at high-risk of COVID-19 in the setting where gold standard diagnostic methods are not available.
Structure Elucidation and Functional Studies of a Novel β-hairpin Antimicrobial Peptide from the Marine Polychaeta Capitella teleta

Endogenous antimicrobial peptides (AMPs) are evolutionary ancient molecular factors of innate immunity that play a key role in host defense. Among the most active and stable under physiological conditions AMPs are the peptides of animal origin that adopt a β-hairpin conformation stabilized by disulfide bridges. In this study, a novel BRICHOS-domain related AMP from the marine polychaeta Capitella teleta, named capitellacin, was produced as the recombinant analogue and investigated. The mature capitellacin exhibits high homology with the known β-hairpin AMP family—tachyplesins and polyphemusins from the horseshoe crabs. The β-hairpin structure of the recombinant capitellacin was proved by CD and NMR spectroscopy. In aqueous solution the peptide exists as monomeric right-handed twisted β-hairpin and its structure does not reveal significant amphipathicity. Moreover, the peptide retains this conformation in membrane environment and incorporates into lipid bilayer. Capitellacin exhibits a strong antimicrobial activity in vitro against a wide panel of bacteria including extensively drug-resistant strains. In contrast to other known β-hairpin AMPs, this peptide acts apparently via non-lytic mechanism at concentrations inhibiting bacterial growth. The molecular mechanism of the peptide antimicrobial action does not seem to be related to the inhibition of bacterial translation therefore other molecular targets may be assumed. The reduced cytotoxicity against human cells and high antibacterial cell selectivity as compared to tachyplesin-1 make it an attractive candidate compound for an anti-infective drug design.
Single-Cell RNA Sequencing of a Postmenopausal Normal Breast Tissue Identifies Multiple Cell Types That Contribute to Breast Cancer

Simple Summary The human body is composed of multiple cell types that form structures and carry out the functions of specific tissues. The human breast is mainly known for the milk ducts organized by epithelial cells, but also contains many other cell types of little-known identity. In this study, we employed the single-cell sequencing technology to ascertain the various cell types present in the normal breast. The results showed 10 distinct cell types that included three epithelial and other novel cell types. The gene signatures of five cell types (three epithelial, one fibroblast subset, and immune cells) matched to the gene expression profiles of >85% breast tumors cataloged in The Cancer Gene Atlas dataset, suggesting their significant contribution to breast cancer. These findings provide a framework for the better mapping of the cellular composition in the breast and its relationship to breast disease. Abstract The human breast is composed of diverse cell types. Studies have delineated mammary epithelial cells, but the other cell types in the breast have scarcely been characterized. In order to gain insight into the cellular composition of the tissue, we performed droplet-mediated RNA sequencing of 3193 single cells isolated from a postmenopausal breast tissue without enriching for epithelial cells. Unbiased clustering analysis identified 10 distinct cell clusters, seven of which were nonepithelial devoid of cytokeratin expression. The remaining three cell clusters expressed cytokeratins (CKs), representing breast epithelial cells; Cluster 2 and Cluster 7 cells expressed luminal and basal CKs, respectively, whereas Cluster 9 cells expressed both luminal and basal CKs, as well as other CKs of unknown specificity. To assess which cell type(s) potentially contributes to breast cancer, we used the differential gene expression signature of each cell cluster to derive gene set variation analysis (GSVA) scores and classified breast tumors in The Cancer Gene Atlas (TGGA) dataset (n = 1100) by assigning the highest GSVA scoring cell cluster number for each tumor. The results showed that five clusters (Clusters 2, 3, 7, 8, and 9) could categorize >85% of breast tumors collectively. Notably, Cluster 2 (luminal epithelial) and Cluster 3 (fibroblast) tumors were equally prevalent in the luminal breast cancer subtypes, whereas Cluster 7 (basal epithelial) and Cluster 9 (other epithelial) tumors were present primarily in the triple-negative breast cancer (TNBC) subtype. Cluster 8 (immune) tumors were present in all subtypes, indicating that immune cells may contribute to breast cancer regardless of the subtypes. Cluster 9 tumors were significantly associated with poor patient survival in TNBC, suggesting that this epithelial cell type may give rise to an aggressive TNBC subset.
Social representation of abuse of persons with severe mental illness in Jakiri, Cameroon: A qualitative study

Background: People with mental illness are vulnerable to abuse in the community. Cultural and social practices may be contributory. Aim: To explore the social representation of abuse of persons with mental illness among the inhabitants of Jakiri municipality in Cameroon. Method: This was a qualitative study based on the Theory of Reasoned Action, conducted in 2018 among 11 inhabitants of Jakiri municipality, aged above 18 years and who had lived in the town for at least 2 years. In-depth face-to-face semi-structured interviews were conducted. Data were analyzed using the basic thematic approach. Results: The belief that mental illness is incurable, a curse from the gods, a result of witchcraft, and a punishment for violation of core social norms were identified as the reasons for physical violence against persons with mental illness. Beliefs that persons with mental illness were disorganized, destructive, physically aggressive, and dependent on others were identified as reasons for emotional abuse. Conclusion: A misconception of mental illness was the major underlying factor for the abuse of persons with mental illness.
T Cell Immunity and the Quest for Protective Vaccines against Staphylococcus aureus Infection

Staphylococcus aureus is a wide-spread human pathogen, and one of the top causative agents of nosocomial infections. The prevalence of antibiotic-resistant S. aureus strains, which are associated with higher mortality and morbidity rates than antibiotic-susceptible strains, is increasing around the world. Vaccination would be an effective preventive measure against S. aureus infection, but to date, every vaccine developed has failed in clinical trials, despite inducing robust antibody responses. These results suggest that induction of humoral immunity does not suffice to confer protection against the infection. Evidence from studies in murine models and in patients with immune defects support a role of T cell-mediated immunity in protective responses against S. aureus. Here, we review the current understanding of the mechanisms underlying adaptive immunity to S. aureus infections and discuss these findings in light of the recent S. aureus vaccine trial failures. We make the case for the need to develop anti-S. aureus vaccines that can specifically elicit robust and durable protective memory T cell subsets.
Phase I Study of Afatinib and Selumetinib in Patients with KRAS-Mutated Colorectal, Non-Small Cell Lung, and Pancreatic Cancer.

LESSONS LEARNED Afatinib and selumetinib can be combined in continuous and intermittent dosing schedules, albeit at lower doses than approved for monotherapy. Maximum tolerated dose for continuous and intermittent schedules is afatinib 20 mg QD and selumetinib 25 mg BID. Since the anticancer activity was limited, we do not recommend to further develop this combination until better biomarkers for response and resistance are defined. BACKGROUND Anti-tumor effects of MEK inhibitors are limited in KRAS-mutated tumors due to feedback activation of upstream epidermal growth factor receptors which reactivates the MAPK and the phosphoinositide 3-kinase (PI3K)-AKT pathway. Therefore, this phase I trial was initiated with the pan-HER inhibitor afatinib plus the MEK inhibitor selumetinib in patients with KRASmt, PIK3CA wild type tumors. METHODS Afatinib and selumetinib were administered according to a 3+3 design in continuous and intermittent schedules. The primary objective was safety, and the secondary objective was clinical efficacy. RESULTS Twenty-six patients were enrolled with colorectal cancer (n = 19), non-small cell lung cancer (NSCLC) (n = 6), and pancreatic cancer (n = 1). Dose-limiting toxicities occurred in six patients, including grade 3 diarrhea, dehydration, decreased appetite, nausea, vomiting, and mucositis. The RP2D was 20 mg afatinib QD and 25 mg selumetinib BID (21 days on/7 days off) for continuous afatinib dosing and for intermittent dosing with both drugs 5 days on/2 days off. Efficacy was limited with disease stabilization for 221 days in a patient with NSCLC as best response. CONCLUSION Afatinib and selumetinib can be combined in continuous and intermittent schedules in patients with KRASmt tumors. Although target engagement was observed, the clinical efficacy was limited.
Does the Predominant Pain Location Influence Functional Outcomes, Satisfaction and Return to Work After Anterior Cervical Discectomy and Fusion for Cervical Radiculopathy?

Study Design. Retrospective review of prospectively-collected registry data. Objectives. The aim of this study was to determine how different combinations of preoperative neck pain (NP) and arm pain (AP) influence functional outcomes, patient satisfaction, and return-to-work in patients undergoing anterior cervical discectomy and fusion (ACDF) for degenerative cervical radiculopathy (DCR). Summary of Background Data. Surgeons often base decisions on the traditional belief that the predominance of radicular upper extremity symptoms is a stronger indication for cervical spine surgery than axial pain. However, there is a paucity of literature supporting this notion. Methods. A prospectively maintained registry was reviewed for all patients who underwent primary ACDF for DCR. Patients were categorized into three groups depending on predominant pain location: AP predominant ([APP]; AP > NP), NP predominant ([NPP]; NP > AP), and equal pain predominance ([EPP]; NP = AP). Patients were prospectively followed for at least 2 years. Results. In total, 303 patients were included: 27.4% APP, 38.9% NPP, and 33.7% EPP cases. The APP group was significantly older (P = 0.030), although there were no other preoperative differences among the three groups. After adjusting for baseline differences, the SF-36 Physical Component Summary was significantly better in the APP group at 6 months (P = 0.048) and 2 years (P = 0.039). In addition, they showed a trend towards better 6-month Neck Disability Index (P = 0.077) and 2-year SF-36 Mental Component Summary (P = 0.059). However, an equal proportion of patients in each group achieved the Minimal Clinically Important Difference for each outcome, were satisfied, and returned to work 2 years after surgery. Conclusion. Although patients with NPP had slightly poorer function and quality of life, all patients experienced a clinically meaningful improvement in patient-reported outcomes, regardless of the predominant pain location. High rates of satisfaction and return-to-work were also achieved. In the context of proper indications, these findings suggest that ACDF can be equally effective for DCR patients with varying combinations of NP or AP. Level of Evidence: 3
Assessing clinical quality performance and staffing capacity differences between urban and rural Health Resources and Services Administration-funded health centers in the United States: A cross sectional study

Background In the United States, there are nearly 1,400 Health Resources and Services Administration-funded health centers (HCs) serving low-income and underserved populations and more than 600 of these HCs are located in rural areas. Disparities in quality of medical care in urban vs. rural areas exist but data on such differences between urban and rural HCs is limited in the literature. We examined whether urban and rural HCs differed in their performance on clinical quality measures before and after controlling for patient, organizational, and contextual characteristics. Methods and findings We used the 2017 Uniform Data System to examine performance on clinical quality measures between urban and rural HCs (n = 1,373). We used generalized linear regression models with the logit link function and binomial distribution, controlling for confounding factors. After adjusting for potential confounders, we found on par performance between urban and rural HCs in all but one clinical quality measure. Rural HCs had lower rates of linking patients newly diagnosed with HIV to care (74% [95% CI: 69%, 80%] vs. 83% [95% CI: 80%, 86%]). We identified control variables that systematically accounted for eliminating urban vs. rural differences in performance on clinical quality measures. We also found that both urban and rural HCs had some clinical quality performance measures that were lower than available national benchmarks. Main limitations included potential discrepancy of urban or rural designation across all HC sites within a HC organization. Conclusions Findings highlight HCs’ contributions in addressing rural disparities in quality of care and identify opportunities for improvement. Performance in both rural and urban HCs may be improved by supporting programs that increase the availability of providers, training, and provision of technical resources.