Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness of Workplace Mediterranean Diet Interventions on Cardiometabolic Risk Factors: A Systematic Review

Background: There are numerous health benefits related to high adherence to the Mediterranean diet (MedDiet), providing a protective effect against cardiometabolic diseases, but there are very few MedDiet studies conducted in the workplace. Therefore, the purpose of this systematic review is to analyze the effectiveness of MedDiet workplace interventions on cardiovascular risk factors. Methods: Studies were identified in four databases: PubMed, Scopus, Web of Science, and CINAHL, published from the earliest time point until 15 May 2021. The inclusion criteria were (a) adults aged 18 to 70 years; (b) MedDiet intervention only; (c) intervention was conducted in a workplace; and (d) the outcomes included measurement of cardiometabolic biomarkers. Exclusion criteria were (a) abstract not in English; (b) full-text non-available; and (c) review articles. Ninety-five studies were retrieved and assessed for inclusion by two independent reviewers, who also used the Cochrane Collaboration Tool to assess study quality and risk of bias. Results: Five high-quality studies were included (n = 436, 89% male). MedDiet interventions carried out within the workplace were effective in improving cardiovascular risk factors such as lipid profile and insulin sensitivity compared with a low-fat diet, especially among obese participants. Blood pressure and inflammatory markers were not improved after the MedDiet interventions. Conclusions: Worksite occupational health teams should consider promoting MedDiet by conducting regular nutritional sessions and providing tailored menus in workplace cafeterias. However, more high-quality studies are necessary to bring more evidence to this topic.
Circulating tumor DNA in primary mediastinal large B-cell lymphoma versus classical Hodgkin lymphoma: a retrospective study

Abstract Few data exist concerning circulating tumor DNA (ctDNA) relevance in primary mediastinal B-cell lymphoma (PMBL). To explore this topic, we applied a 9-gene next-generation sequencing pipeline to samples from forty-four PMBL patients (median age 36.5 years). The primary endpoint was a similarity between paired biopsy/plasma mutational profiles. We detected at least one variant in 32 plasma samples (80%). The similarity between the biopsy and ctDNA genetic profiles for the 30 patients with paired mutated biopsy/plasma samples was greater than or equal to 80% in 19 patients (63.3%). We then compared PMBL ctDNA features with those of a cohort of Hodgkin lymphoma patients (n = 60). The top three mutated genes were SOCS1, TNFAIP3, and B2M in both lymphoma types. PMBL displayed more alterations in TNFAIP3 (71.9% vs. 46.3%, p = 0.029) and GNA13 (46.9% vs. 17.1%, p = 0.013) than cHL. Our 9-gene set may delineate tumor genotypes using ctDNA samples from both lymphoma types.
The Rubber Hand Illusion: Top-down attention modulates embodiment

The Rubber Hand Illusion (RHI) creates distortions of body ownership through multimodal integration of somatosensory and visual inputs. This illusion largely rests on bottom-up (automatic multisensory and perceptual integration) mechanisms. However, the relative contribution from top-down factors, such as controlled processes involving attentional regulation, remains unclear. Following previous work that highlights the putative influence of higher-order cognition in the RHI, we aimed to further examine how modulations of working memory load and task instructions—two conditions engaging top-down cognitive processes—influence the experience of the RHI, as indexed by a number of psychometric dimensions. Relying on exploratory factor analysis for assessing this phenomenology within the RHI, our results confirm the influence of higher-order, top-down mental processes. Whereas task instruction strongly modulated embodiment of the rubber hand, cognitive load altered the affective dimension of the RHI. Our findings corroborate that top-down processes shape the phenomenology of the RHI and herald new ways to improve experimental control over the RHI.
Modulation of pacemaker channel function in a model of thalamocortical hyperexcitability by demyelination and cytokines

Abstract A consensus is yet to be reached regarding the exact prevalence of epileptic seizures or epilepsy in multiple sclerosis (MS). In addition, the underlying pathophysiological basis of the reciprocal interaction among neuroinflammation, demyelination, and epilepsy remains unclear. Therefore, a better understanding of cellular and network mechanisms linking these pathologies is needed. Cuprizone-induced general demyelination in rodents is a valuable model for studying MS pathologies. Here, we studied the relationship among epileptic activity, loss of myelin, and pro-inflammatory cytokines by inducing acute, generalized demyelination in a genetic mouse model of human absence epilepsy, C3H/HeJ mice. Both cellular and network mechanisms were studied using in vivo and in vitro electrophysiological techniques. We found that acute, generalized demyelination in C3H/HeJ mice resulted in a lower number of spike–wave discharges, increased cortical theta oscillations, and reduction of slow rhythmic intrathalamic burst activity. In addition, generalized demyelination resulted in a significant reduction in the amplitude of the hyperpolarization-activated inward current (Ih) in thalamic relay cells, which was accompanied by lower surface expression of hyperpolarization-activated, cyclic nucleotide-gated channels, and the phosphorylated form of TRIP8b (pS237-TRIP8b). We suggest that demyelination-related changes in thalamic Ih may be one of the factors defining the prevalence of seizures in MS.
Intensive care‐related cognitive impairment: A biopsychosocial overview

Advancements in critical care medicine have improved survival rates for patients experiencing critical illness in intensive care units (ICUs). Although mortality has declined, more than half of ICU survivors experience functional impairments that persist beyond discharge. Of particular concern is ICU‐related cognitive impairment, which can extend across the care continuum, ranging from acute and transient presentations in the ICU (eg, delirium) to long‐term impairments years after discharge. ICU‐related cognitive impairment has received increased attention in the literature, particularly as it relates to ICU survivors who have received and survived critical care in the context of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic and are now experiencing postacute sequelae of SARS‐CoV‐2 infection. The medical complexity and heterogeneity of ICU survivors, coupled with the multifactorial etiology of ICU‐related cognitive impairments, lead to challenges in how to optimize care for ICU survivors at various stages of recovery. This review aims to provide an overview of cognitive outcomes associated with critical illness by integrating recent literature focused on etiology, assessment, and interventions in the context of ICU‐related cognitive impairments. The narrative review employs a biopsychosocial framework to comprehensively evaluate the multifactorial nature of ICU‐related cognitive outcomes. Authors also highlight that multidisciplinary teams composed of key rehabilitation providers are likely best suited for optimizing recovery trajectories of ICU survivors.
Human brain activity and functional connectivity as memories age from one hour to one month

ABSTRACT Theories of memory consolidation suggest the role of brain regions and connectivity between brain regions change as memories age. Human lesion studies indicate memories become hippocampus-independent over years, whereas animal studies suggest this process occurs across relatively short intervals, from days to weeks. Human neuroimaging studies suggest that changes in hippocampal and cortical activity and connectivity can be detected over these short intervals, but many of these studies examined only two time periods. We examined memory and fMRI activity for photos of indoor and outdoor scenes across four time periods to examine these neural changes more carefully. Participants (N = 21) studied scenes 1 hour, 1 day, 1 week, or 1 month before scanning. During scanning, participants viewed scenes, made old/new recognition memory judgments, and gave confidence ratings. Memory accuracy, confidence ratings, and response times changed with memory age. Brain activity in a widespread cortical network either increased or decreased with memory age, whereas hippocampal activity was not related to memory age. These findings were almost identical when effects of behavioral changes across time periods were minimized. Functional connectivity of the ventromedial prefrontal cortex with the posterior parietal cortex increased with memory age. By contrast, functional connectivity of the hippocampus with the parahippocampal cortex and fusiform gyrus decreased with memory age. In sum, we detected changes in cortical activity and changes in hippocampal and cortical connectivity with memory age across short intervals. These findings provide support for the predictions of systems consolidation and suggest that these changes begin soon after memories are formed.
Engineering Acetobacterium woodii for the production of isopropanol and acetone from carbon dioxide and hydrogen

The capability of four genetically modified Acetobacterium woodii strains for improved production of acetone from CO2 and hydrogen was tested. The acetone biosynthesis pathway was constructed by combining genes from Clostridium acetobutylicum and Clostridium aceticum. Expression of acetone production genes was demonstrated in all strains. In bioreactors with continuous gas supply, all produced acetic acid, acetone, and, surprisingly, isopropanol. The production of isopropanol was caused by an endogenous secondary alcohol dehydrogenase (SADH) activity at low gas‐feeding rate. Although high amounts of the natural end product acetic acid of A. woodii were formed,14.5 mM isopropanol and 7.6 mM acetone were also detected, showing that this is a promising approach for the production of new solvents from C1 gases. The highest acetic acid, acetone, and isopropanol production was detected in the recombinant A. woodii [pJIR750_ac1t1] strain, with final concentrations of 438 mM acetic acid, 7.6 mM acetone, and 14.5 mM isopropanol. The engineered strain A. woodii [pJIR750_ac1t1] was found to be the most promising strain for acetone production from a gas mixture of CO2 and H2 and the formation of isopropanol in A. woodii was shown for the first time.
Weekly near-peer tutoring sessions improve students’ performance on basic medical sciences and USMLE Step1 examinations

Abstract Purpose This study examined the relationship between attendance at weekly near-peer tutoring (NPT) sessions offered in the second year of medical school and academic performance on basic science and USMLE Step 1 examinations. Methods Twenty-four weekly NPT sessions were delivered across all modules in the second year of medical school. Attendance of the sessions was recorded and students were divided into three groups: high (16–24 sessions), moderate (7–15 sessions), and low-no (0–6 sessions) attendance groups. Pearson product-moment correlation coefficient was computed to determine the relationship between students’ frequency of attendance and their performance on overall basic sciences, two NBME CBSEs, and USMLE Step 1 examinations. Students’ academic performance was also analyzed using ANOVA and Bonferroni post hoc test (p < 0.05) to compare differences between the three groups. Results Pearson correlation analyses revealed that attending peer tutoring sessions was significantly correlated with students’ performance in overall basic sciences, CBSE mid-year, CBSE final, and USMLE Step 1 examinations. The high attendance groups significantly outperformed the low-no attendance groups on overall basic sciences (p = 0.007), CBSE mid-year (p < 0.001), CBSE final (p < 0.018), and USMLE Step 1 (p = 0.048) examinations. Conclusions Attending NPT sessions are significantly correlated with students’ performance on basic sciences and on USMLE Step1 examinations. Attendance of weekly NPT sessions is a valuable experience for M2 students.
Changes in female function and autonomous selfing across floral lifespan interact to drive variation in the cost of selfing

Abstract Premise Morphological and developmental changes as flowers age can impact patterns of mating. At the same time, direct or indirect costs of floral longevity can alter their fitness outcomes. This influence has been less appreciated, particularly with respect to the timing of selfing. We investigated changes in stigma events, autonomous selfing, outcross seed set capacity, and autofertility—a measure representing the potential for reproductive assurance—across floral lifespan in the mixed‐mating biennial Sabatia angularis. Methods We examined stigma morphology and receptivity, autonomous self‐pollen deposition, and seed number and size under autonomous self‐pollination and hand outcross‐pollination for flowers of different ages, from 1 d of female phase until 14 d. We compared autonomous seed production to maximal outcross seed production at each flower age to calculate an index of autofertility. Results The stigmatic lobes begin to untwist 1 d post anthesis. They progressively open, sextend, coil, and increase in receptivity, peaking or saturating at 8–11 d, depending on the measure. Autonomous seed production can occur early, but on average remains low until 6 d, when it doubles. In contrast, outcross seed number and size start out high, then decline precipitously. Consequently, autofertility increases steeply across floral lifespan. Conclusions Changes in stigma morphology and receptivity, timing of autonomous self‐pollen deposition, and floral senescence can interact to influence the relative benefit of autonomous selfing across floral lifespan. Our work highlights the interplay between evolution of floral longevity and the mating system, with implications for the maintenance of mixed mating in S. angularis.
A novel mode of action for COX‐2 inhibition: Targeting ATPase domain of HSP90 induces ubiquitin degradation of new client protein COX‐2

Dear Editor, Cyclooxygenase 2 (COX-2) is the main target of nonsteroidal anti-inflammatory drugs (NSAIDs),1 and it is rapidly expressed in response to extracellular factor stimulation like lipopolysaccharide (LPS) in mouse monocyte macrophage 264.7 (RAW264.7) cells.2 Herein,we reveal the existence of a novel mechanism that intervenes the formation of the heat shock protein 90 (HSP90)/COX-2 complex and induces the ubiquitin-proteasomal degradation of COX-2. Baicalein, the aglycone of baicalin, is a key antipyretic component of the classic traditional Chinese medicinal herb Scutellaria baicalensis Georgi (Huangqin),3 showed better antipyretic effects and nitric oxide inhibition than baicalin (Figure 1A-C). We synthesized and evaluated several molecular probes based on baicalein (Figure 1D, Figures S1-S7), and the potential targets captured by baicalein probe modified magnetic microspheres were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, protein profiling analysis, and cell co-localization imaging (Figure 1E-G). The results of these analyses showed that HSP90 was the most likely target of baicalein. HSP90, the most common chaperone protein, could help its client proteins to fold correctly to exert their biological activity.4 Then, two known client proteins of HSP90—JNK and AKT—were dephosphorylated by baicalein (Figure 1H). The binding affinity between baicalein and HSP90, as detected by surface plasmon resonance (SPR), was approximately 26.07 μM (Figure 2A, Figure S8), while baicalin could not bind to HSP90 (Figure S9). The adenosine triphosphatase (ATPase) domain is considered the most important in HSP90. When HSP90 binds to adenosinetriphosphate (ATP), transient dimerization occurs in the N-terminal region, leading to HSP90 inactivation.5 The binding affinity between ATP and HSP90 was 0.6 mM, as detected by SPR; this affinity increased approximately six-fold to 3.5 mM when baicalein competed with ATP
The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in non-human primates and has an extended half-life in humans

Despite the success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of coronavirus disease 2019 (COVID-19). Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19 and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct, nonoverlapping epitopes on the spike protein receptor binding domain to neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and reduce effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry, and neutralize all tested SARS-CoV-2 variants of concern. In a nonhuman primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, whereas therapeutic administration accelerated virus clearance from the lung. In an ongoing phase 1 study in healthy participants (NCT04507256), a 300-mg intramuscular injection of AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers greater than 10-fold above those of convalescent serum for at least 3 months, which remained threefold above those of convalescent serum at 9 months after AZD7442 administration. About 1 to 2% of serum AZD7442 was detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentration suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19. Description AZD7442 neutralizes SARS-CoV-2, has prophylactic and therapeutic efficacy in NHPs, and is projected to contribute to long-term human protection. Long-lasting antibodies Although monoclonal antibody therapeutics have considerably improved outcomes for individuals with COVID-19, their utility as a prophylactic intervention is restricted by the emergence of variants of concern (VOCs) and by short half-lives. To address this, Loo et al. evaluated a pair of antibodies, collectively termed AZD7442, which bind to two distinct epitopes on the receptor binding domain of the SARS-CoV-2 spike protein and have been modified to have an extended half-life. The antibody combination protected nonhuman primates from infection with SARS-CoV-2 when administered prophylactically or therapeutically. The antibodies were also resistant to all tested VOC, including the delta variant. Last, the authors showed that AZD7442 administration to healthy adults resulted in neutralizing antibody titers that were projected to confer long-term protection.
Association of Timing for Starting Dual Antiplatelet Treatment With Cilostazol and Recurrent Stroke

Background and Objectives Long-term treatment with the combination of cilostazol with aspirin or clopidogrel showed a lower risk of stroke recurrence compared to aspirin or clopidogrel alone after high-risk noncardioembolic ischemic stroke in a randomized trial. We aimed to determine whether the effect of the dual medication compared to monotherapy on risk of recurrent ischemic stroke differs according to timing of starting medication after stroke onset. Methods In a subanalysis of the randomized controlled trial, patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone or a combination of cilostazol with aspirin or clopidogrel. They were divided into 3 groups according to the timing of starting trial treatment: between 8 and 14 days after stroke onset (8–14 days group), between 15 and 28 days after stroke onset (15–28 days group), and between 29 and 180 days after stroke onset (29–180 days group). The primary efficacy outcome was the first recurrence of ischemic stroke. Safety outcomes included severe or life-threatening bleeding. Results Of 1,879 patients, 498 belonged to the 8–14 days group, 467 to the 15–28 days group, and 914 to the 29–180 days group. There was a significant treatment-by-subgroup interaction for the recurrence of ischemic stroke between trial treatment and trichotomized groups. The recurrence of ischemic stroke was less common with dual therapy than with monotherapy in the 15–28 days group (annualized rate 1.5% vs 4.9%, respectively; adjusted hazard ratio 0.34 [95% CI 0.12–0.95]) and the 29–180 days group (1.9% vs 4.4%, respectively; 0.27 [0.12–0.63]) and similarly common in the 8–14 days group (4.5% for both; 1.02 [0.51–2.04]). Severe or life-threatening bleeding occurred similarly between patients on dual therapy and those on monotherapy in any of the trichotomized groups (crude hazard ratio 0.22 [95% CI 0.03–1.88] in the 8–14 days group, 1.07 [0.15–7.60] in the 15–28 days group, and 0.76 [0.24–2.39] in the 29–180 days group). Discussion Long-term dual antiplatelet therapy using cilostazol starting 15–180 days after stroke onset, compared to therapy started 8–14 days after onset, was more effective for secondary stroke prevention than monotherapy without increasing hemorrhage risk. Trial Registration Information ClinicalTrials.gov NCT01995370; UMIN Clinical Trials Registry 000012180. Classification of Evidence This study provides Class II evidence that for patients with acute noncardioembolic stroke taking either aspirin or clopidogrel, the addition of cilostazol 15–180 days after stroke onset decreases the risk of recurrent ischemic stroke.
Evaluation of potential drug-drug interactions in cancer patients at a tertiary care hospital in Pakistan

Background Despite harboring a high burden of cancer patients who are at high risk of potential drug-drug interactions (pDDIs), there is scarcity of published information about pDDIs in cancer patients from Pakistan. Objective To evaluate frequency, pattern, mechanism and factors associated with pDDIs in cancer patients treated at a tertiary care hospital in Pakistan. Methods In this cross-sectional analytical study, a total of 253 eligible ambulatory cancer patients treated at Center for Nuclear Medicine and Radiotherapy Hospital Quetta were evaluated for pDDIs using IBM Micromedex® Drug Interactions. SPSS (version 26) was used for conducting multivariate analysis to find factors associated with the presence pDDIs. A p-value <0.05 was considered statistically significant. Results A total of 141/253 (55.7%) patients were exposed to at-least one pDDI. A total of 251 pDDIs were noted with a median of one pDDI/per patient (interquartile range:1–2) Majority interactions were of major severity (72.9%), pharmacodynamic (49.8%) and had fair documentation level (64.1%). Anti-cancer drugs were involved in 73.0% pDDIs with doxorubicin as the most commonly involved (40.0%) anti-cancer followed by cyclophosphamide (27.6%) and cisplatin (13.5%). Potential cardiac adverse events made the bulk (33.8%) of predicted events. Receiving >2 anti-cancer (OR = 5.19, p-value = 0.001) and >6 ancillary drugs (OR = 4.16, p-value = 0.033) emerged as the risk factors of pDDIs. Conclusions The prevalence of pDDIs was within the range reported in published literature. Solid medication review, availability of DDI detecting tools and clinical pharmacist, and paying special attention to the high-risk patients may reduce the frequency of pDDIs at the study site.