Miracle-dz/UniFAR-FTUs huggingface dataset:
Update on infective complications in patients treated with alemtuzumab for multiple sclerosis: review and meta-analysis of real-world and randomized studies

ABSTRACT Objective We aimed to systematically assess the pooled prevalence of infective complications in randomized controlled trials (RCTs) and real-world studies (RWSs) investigating alemtuzumab treatment in multiple sclerosis (MS), also looking at selected infections and their severity. Methods We included in the analysis RCTs and RWSs investigating the use of alemtuzumab in MS in which infective complications were reported, as well as case reports of rare infections. We conducted a meta-analysis of proportions and a random effect model meta-regression to investigate heterogeneity. Results The pooled prevalence of infective complications in alemtuzumab treated MS patients is 24%. The most common reported infections are respiratory tract infections (47%) and the most part of the infections are mild-to-moderate (85%). Severe infections account for 6% of the total estimate. We found first-time-reported cases of invasive aspergillosis, hepatitis E virus infection, EBV hepatitis, and cerebral toxoplasmosis. The prevalence of infections is higher in studies conducted before 2009, and in studies with higher proportion of male participants. Conclusions Clinicians should be aware that the prevalence of serious infections during alemtuzumab can be higher than expected from RCTs. Peculiar opportunistic infections should be considered when evaluating a patient treated with alemtuzumab who develops signs of infection.
Impact of hypoxia on the pathogenesis and therapy resistance in multiple myeloma

Multiple myeloma (MM) is a refractory plasma cell tumor. In myeloma cells, the transcription factor IRF4, the master regulator of plasma cells, is aberrantly upregulated and plays an essential role in oncogenesis. IRF4 forms a positive feedback loop with MYC, leading to additional tumorigenic properties. In recent years, molecular targeted therapies have contributed to a significant improvement in the prognosis of MM. Nevertheless, almost all patients experience disease progression, which is thought to be a result of treatment resistance induced by various elements of the bone marrow microenvironment. Among these, the hypoxic response, one of the key processes for cellular homeostasis, induces hypoxia‐adapted traits such as undifferentiation, altered metabolism, and dissemination, leading to drug resistance. These inductions are caused by ectopic gene expression changes mediated by the activation of hypoxia‐inducible factors (HIFs). By contrast, the expression levels of IRF4 and MYC are markedly reduced by hypoxic stress. Notably, an anti‐apoptotic capability is usually acquired under both normoxic and hypoxic conditions, but the mechanism is distinct. This fact strongly suggests that myeloma cells may survive by switching their dependent regulatory factors from IRF4 and MYC (normoxic bone marrow region) to HIF (hypoxic bone marrow microenvironment). Therefore, to achieve deep remission, combination therapeutic agents, which are complementarily effective against both IRF4‐MYC‐dominant and HIF‐dominated fractions, may become an important therapeutic strategy for MM.
Collective memory for American leaders: Measuring recognition for the names and faces of the US presidents

Collective memory studies show that Americans remember their presidents in a predictable pattern, which can be described as a serial position curve with an additional spike for Abraham Lincoln. However, all prior studies have tested Americans’ collective memory for the presidents by their names. How well do Americans know the faces of the presidents? In two experiments, we investigated presidential facial recognition and compared facial recognition to name recognition. In Experiment 1, an online sample judged whether each of the official portraits of the US presidents and similar portraits of nonpresidents depicted a US president. The facial recognition rate (around 60%) was lower than the name recognition rate in past research (88%), but the overall pattern still fit a serial position curve. Some nonpresidents, such as Alexander Hamilton, were still falsely identified as presidents at high rates. In Experiment 2, a college sample completed a recognition task composed of both faces and names to directly compare the recognition rates. As predicted, subjects recognized the names of the presidents more frequently than the faces. Some presidents were frequently identified by their names but not by their faces (e.g. John Quincy Adams), while others were the opposite (e.g. Calvin Coolidge). Together, our studies show that Americans’ memory for the faces of the presidents is somewhat worse than their memory for the names of the presidents but still follows the same pattern, indicating that collective memories contain more than just verbal information.
A prospective, phase II, single-centre, cross-sectional, randomised study investigating Dehydroepiandrosterone supplementation and its Profile in Trauma: ADaPT

Introduction The improvements in short-term outcome after severe trauma achieved through early resuscitation and acute care can be offset over the following weeks by an acute systemic inflammatory response with immuneparesis leading to infection, multiorgan dysfunction/multiorgan failure (MOF) and death. Serum levels of the androgen precursor dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, steroids with immune-enhancing activity, are low after traumatic injury at a time when patients are catabolic and immunosuppressed. Addressing this deficit and restoring the DHEA(S) ratio to cortisol may provide a range of physiological benefits, including immune modulatory effects. Objective Our primary objective is to establish a dose suitable for DHEA supplementation in patients after acute trauma to raise circulating DHEA levels to at least 15 nmol/L. Secondary objectives are to assess if DHEA supplementation has any effect on neutrophil function, metabolic and cytokine profiles and which route of administration (oral vs sublingual) is more effective in restoring circulating levels of DHEA, DHEAS and downstream androgens. Methods and analysis A prospective, phase II, single-centre, cross-sectional, randomised study investigating Dehydroepiandrosterone supplementation and its profile in trauma, with a planned recruitment between April 2019 and July 2021, that will investigate DHEA supplementation and its effect on serum DHEA, DHEAS and downstream androgens in trauma. A maximum of 270 patients will receive sublingual or oral DHEA at 50, 100 or 200 mg daily over 3 days. Females aged ≥50 years with neck of femur fracture and male and female major trauma patients, aged 16–50 years with an injury severity score ≥16, will be recruited. Ethics and dissemination This protocol was approved by the West Midlands – Coventry and Warwickshire Research Ethics Committee (Reference 18/WM/0102) on 8 June 2018. Results will be disseminated via peer-reviewed publications and presented at national and international conferences. Trial registration This trial is registered with the European Medicines Agency (EudraCT: 2016-004250-15) and ISRCTN (12961998). It has also been adopted on the National Institute of Health Research portfolio (CPMS ID:38158). Trial progression The study recruited its first patient on 2 April 2019 and held its first data monitoring committee on 8 November 2019. DHEA dosing has increased to 100 mg in both male cohorts and remains on 50 mg in across all female groups.
Identification, Synthesis, and Strategy For Minimization of Potential Impurities Observed In Raltegravir Potassium Drug Substance

Multiple sources of anticipated degradation and process impurities of raltegravir potassium drug substance observed during the laboratory optimization and later during its bulk synthesis are described in this article. The impurities were monitored by UPLC, and their structures are tentatively assigned on the basis of fragmentation patterns in LC–MS and NMR spectroscopy. Most of the impurities are synthesized, and their assigned constitutions were confirmed by co-injection in UPLC. In addition to the formation, synthesis, and characterization, strategy for minimizing these impurities to the level accepted by ICH is also described. We feel that our study will be helpful to the generic industry for obtaining chemically pure raltegravir potassium.
Demonstrating the feasibility of digital health to support pediatric patients in South Africa

Resources for management of epilepsy in Africa are extremely limited reinforcing the need to develop innovative strategies for optimizing care. Studies have shown that the prevalence of epilepsy in low‐ and middle‐income countries is substantially greater than in more resourced countries. The objective of this report was to demonstrate that mobile Health (mHealth) technologies have the potential to improve the management of epilepsy in Africa.
Same day endoscopic retrograde cholangio-pancreatography immediately after endoscopic ultrasound for choledocholithiasis is feasible, safe and cost-effective

Abstract Background Patients with suspected choledocholithiasis should undergo further confirmatory imaging test by endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography (MRCP) before performing definite extraction by endoscopic retrograde cholangiopancreatography (ERCP). Usually, those procedures are performed at a separate session. Aim The aim of our study is to report the safety, efficacy and cost-effectiveness of same day EUS and ERCP. Methods A retrospective study including all patients who underwent EUS and ERCP for choledocholithiasis from 1st January 2020 through 1st January 2021. Patients were categorized into same day EUS and ERCP (group A) and separate day procedures (group B). Univariate descriptive analysis was done to compare between the groups and cost-effectiveness analysis was based on the length of hospitalization. Results Sixty-one patients (57.5%) underwent same day EUS and ERCP (group A), as compared to 45 patients (42.5%) who had separate sessions (group B). The average ages in groups A and B were 66.1 ± 20.7 years and 65.8 ± 19.3 years, respectively (p = .47). There was no difference in the mean doses of midazolam, propofol and fentanyl in EUS and ERCP examinations in both groups. Notably, group A had a significantly lower hospitalization length as compared to group B (7.4 ± 2.9 vs. 9.7 ± 3.9 days, p = .0003). Consequently, same day EUS and ERCP was associated with a significant cost saving as compared to group B (7680.9$ ± 3071.4$vs 10089.4$±4053.4$, p = .0003), respectively. There was no serious anesthesia related adverse events. Conclusion Same day EUS and ERCP for choledocholithiasis was safe and cost-effective with significant lower hospitalization length.
Digital Phenotyping in Child and Adolescent Psychiatry: A Perspective

Supplemental digital content is available in the text. Abstract Digital phenotyping (DP) provides opportunities to study child and adolescent psychiatry from a novel perspective. DP combines objective data obtained from digital sensors with participant-generated “active data,” in order to understand better an individual’s behavior and environmental interactions. Although this new method has led to advances in adult psychiatry, its use in child psychiatry has been more limited. This review aims to demonstrate potential benefits of DP methodology and passive data collection by reviewing studies specifically in child and adolescent psychiatry. Twenty-six studies were identified that collected passive data from four different categories: accelerometer/actigraph data, physiological data, GPS data, and step count. Study topics ranged from the associations between manic symptomology and cardiac parameters to the role of daily emotions, sleep, and social interactions in treatment for pediatric anxiety. Reviewed studies highlighted the diverse ways in which objective data can augment naturalistic self-report methods in child and adolescent psychiatry to allow for more objective, ecologically valid, and temporally resolved conclusions. Though limitations exist—including a lack of participant adherence and device failure and misuse—DP technology may represent a new and effective method for understanding pediatric cognition, behavior, disease etiology, and treatment efficacy.
Local excitons in Si/Ge inverted quantum huts (IQHs) embedded Si

We investigate the properties of excitons in the SiGe inverted quantum huts (IQHs) embedded in Si employing high-resolution x-ray photoemission spectroscopy. Ultra-small Si/Ge IQHs (13.3 nm × 6.6 nm) were grown on a Si buffer layer deposited on a Si (001) substrate using molecular beam epitaxy. We study the behavior of the excitons at different depths of the IQH structures by exposing the desired surfaces via controlled sputtering and annealing processes. The Si and Ge core level spectra show interesting properties at different surfaces; additionally, we discover distinct new features at the lower binding energy side of the Ge 3d peak. The emergence of these features is attributed to the final state effects arising from core hole screening by the excitons. The properties of these features in the spectra collected at different locations of the IQHs are found significantly different from each other, indicating the local character of the excitons. These results provide a pathway to study the properties of excitons in such quantum structures. The evidence of the local character of the excitons suggests a type I behavior of the system, which is important for the devices for optoelectronic applications, quantum communications, etc.
A combination of fecal calprotectin and human beta-defensin 2 facilitates diagnosis and monitoring of inflammatory bowel disease

ABSTRACT Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) show a large overlap in clinical presentation, which presents diagnostic challenges. As a consequence, invasive and burdensome endoscopies are often used to distinguish between IBD and IBS. Here, we aimed to develop a noninvasive fecal test that can distinguish between IBD and IBS and reduce the number of endoscopies. We used shotgun metagenomic sequencing to analyze the composition and function of gut microbiota of 169 IBS patients, 447 IBD patients and 1044 population controls and measured fecal Calprotectin (FCal), human beta defensin 2 (HBD2), and chromogranin A (CgA) in these samples. These measurements were used to construct training sets (75% of data) for logistic regression and machine learning models to differentiate IBS from IBD and inactive from active IBD. The results were replicated on test sets (remaining 25% of the data) and microbiome data obtained using 16S sequencing. Fecal HBD2 showed high sensitivity and specificity for differentiating between IBD and IBS (sensitivity = 0.89, specificity = 0.76), while the inclusion of microbiome data with biomarkers (HBD2 and FCal) showed a potential for improvement in predictive power (optimal sensitivity = 0.87, specificity = 0.93). Shotgun sequencing–based models produced comparable results using 16S-sequencing data. HBD2 and FCal were found to have predictive power for IBD disease activity (AUC ≈ 0.7). HBD2 is a novel biomarker for IBD in patients with gastro-intestinal complaints, especially when used in combination with FCal and potentially in combination with gut microbiome data.
Organic cultivation practices enhanced antioxidant activities and secondary metabolites in giant granadilla (Passiflora quadrangularis L.)

Passiflora quadrangularis L. belongs to the family Passifloraceae which bears larger fruit with edible juicy mesocarp and pulp known as a good source of phytochemicals. Cultivation and plant management practices are known to influence the phytochemical compositions of agricultural produce. This study aimed to examine the influence of the cultivation practices on the antioxidant activities and secondary metabolites of the organically and conventionally grown P. quadrangularis. Findings revealed organically treated P. quadrangularis plants showed enhancement in their antioxidant properties and secondary metabolites profiles. Among the plant parts, leaves of P. quadrangularis grown organically possessed higher antioxidant activities compared to the conventional in all assays evaluated. The antioxidant activities in the edible parts of the P. quadrangularis fruit have also been enhanced through organic cultivation with significantly higher total phenolic content and DPPH in mesocarp, and the pulp showed higher total flavonoid content, DPPH and FRAP. This observation is supported by a higher level of vitamins and secondary metabolites in the samples. The secondary metabolites profile showed mesocarps were phenolic rich, the pulps were flavonoids rich while leaves showed good composition of phenolics, flavonoids and terpenoids with outstanding antioxidant activities. The common secondary metabolites for organically produced P. quadrangularis in different plant parts include 2-isopropyl-3-methoxycinnamic acid (mesocarp and pulp), myricetin isomers (pulp and leaves), and malvidin-3-O-arabinoside isomers (pulp and leaves). This study confirmed that organic cultivated P. quadrangularis possessed higher antioxidant activities contributed by its vitamins and secondary metabolites.
Healthcare utilisation, cancer screening and potential barriers to accessing cancer care in rural South West Nigeria: a cross-sectional study

Background/aims Cancer burden is predicted to double by 2030 in sub-Saharan Africa; access to healthcare services for cancer management is a priority in the region. In Nigeria, National Cancer Control Plan aims to ensure >50% cancer screening of eligible populations by 2022 for all Nigerians. We describe healthcare utilisation, cancer screening activities and potential barriers to accessing cancer care within an understudied rural community-based adult population in South West Nigeria. Methods In April 2018, we conducted a cross-sectional study of community-based adults (>18 years) ~130 km east of Ibadan, 250 km from Lagos in Osun State, South West Nigeria. Participants completed a face-to-face survey in local dialect. We used a questionnaire to assess demographics, health status, income, medical expenditures, doctor visits and cancer screening history. Results We enrolled 346 individuals: with median age of 52 years and 75% women. Of the entire cohort, 4% had medical insurance. 46% reported a major medical cost in the last year. Cancer screening activities were infrequent in eligible participants: 1.5% reported having had cervical cancer screening, 3.3% mammogram and 5% colonoscopy screening. Cancer screening assessment was less frequent in those with less income and lower education levels. Using a multivariable logistic regression model including personal income, insurance status and education, higher personal income was associated with more cancer screening activity (OR 2.7, 95% CI 1.3 to 5.7, p<0.01). Despite this, most individuals had contact with a primary healthcare doctor (52% in the last year), and over 70% access to radio and TV suggesting the opportunity to expand community-based screening interventions and awareness exists. Conclusions Despite national increases in cancer cases, we highlight a deficiency in cancer screening and universal healthcare coverage within a community-based adult Nigerian population. Subject to availability of governmental resources, increasing financial risk protection, awareness and targeted resource allocation may help expand access in Nigeria.
Four-Second Power Cycling Training Increases Maximal Anaerobic Power, Peak Oxygen Consumption, and Total Blood Volume

ABSTRACT Introduction High-intensity interval training is an effective tool to improve cardiovascular fitness and maximal anaerobic power. Different methods of high-intensity interval training have been studied but the effects of repeated maximal effort cycling with very short exercise time (i.e., 4 s) and short recovery time (15–30 s) might suit individuals with limited time to exercise. Purpose We examined the effects of training at near maximal anaerobic power during cycling (PC) on maximal anaerobic power, peak oxygen consumption (V˙O2peak), and total blood volume in 11 young healthy individuals (age: 21.3 ± 0.5 yr) (six men, five women). Methods Participants trained three times a week for 8 wk performing a PC program consisting of 30 bouts of 4 s at an all-out intensity (i.e., 2 min of exercise per session). The cardiovascular stress progressively increased over the weeks by decreasing the recovery time between sprints (30–24 s to 15 s), and thus, total session time decreased from 17 to <10 min. Results Power cycling elicited a 13.2% increase in V˙O2peak (Pre: 2.86 ± 0.18 L·min−1, Post: 3.24 ± 0.21 L·min−1; P = 0.003) and a 7.6% increase in total blood volume (Pre: 5139 ± 199 mL, Post: 5529 ± 342 mL; P < 0.05). Concurrently, maximal anaerobic power increased by 17.2% (Pre: 860 ± 53 W, Post: 1,009 ± 71 W; P < 0.001). Conclusions A PC training program employing 30 bouts of 4 s duration for a total of 2 min of exercise, resulting in a total session time of less than 10 min in the last weeks, is effective for improving total blood volume, V˙O2peak and maximal anaerobic power in young healthy individuals over 8 wk. These observations require reconsideration of the minimal amount of exercise needed to significantly increase both maximal aerobic and anaerobic power.
Cannabinoids, their cellular receptors, and effects on the invasive phenotype of carcinoma and metastasis

The morbidity and mortality of cancer are significantly impacted by the invasive and metastatic potential of particular subgroups of malignant cells within a tumor. The particular pre‐metastatic properties of cancerous cells are thus a critical target for novel therapeutics in the oncology field. Cannabinoid molecules have been investigated in recent years in the context of invasion and metastasis of various malignancies, with varying effects reported in the literature.
Plasma membrane calcium ATPase downregulation in dopaminergic neurons alters cellular physiology and motor behaviour in Drosophila melanogaster

The accumulation of Ca2+ and its subsequent increase in oxidative stress is proposed to be involved in selective dysfunctionality of dopaminergic neurons, the main cell type affected in Parkinson's disease. To test the in vivo impact of Ca2+ increment in dopaminergic neurons physiology, we downregulated the plasma membrane Ca2+ ATPase (PMCA), a pump that extrudes cytosolic Ca2+, by expressing PMCARNAi in Drosophila melanogaster dopaminergic neurons. In these animals, we observed major locomotor alterations paralleled to higher cytosolic Ca2+ and increased levels of oxidative stress in mitochondria. Interestingly, although no overt degeneration of dopaminergic neurons was observed, evidences of neuronal dysfunctionality were detected such as increases in presynaptic vesicles in dopaminergic neurons and in the levels of dopamine in the brain, as well as presence of toxic effects when PMCA was downregulated in the eye. Moreover, reduced PMCA levels were found in a Drosophila model of Parkinson's disease, Parkin knock‐out, expanding the functional relevance of PMCA reduction to other Parkinson's disease‐related models. In all, we have generated a new model to study motor abnormalities caused by increments in Ca2+ that lead to augmented oxidative stress in a dopaminergic environment, added to a rise in synaptic vesicles and dopamine levels.