Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Circulating Tumor Cells in Chemoresistant Metastatic Breast Cancer

Breast cancer is the most frequent form of cancer among women and is one of the leading causes of death. Two routes of the metastatic process have been described: linear and parallel progression. A key factor is represented by circulating tumor cells (CTCs). CTCs detach from the primary tumor or develop from cancer stem cells (CSCs) that undergo epithelial-to-mesenchymal transition (EMT). CTCs migrate to the distant site where the reverse process occurs and a new tumor arises. One of the key problems of metastatic disease is chemoresistance, which leads to treatment failure and, eventually, death. The aim of this review is to present up-to-date data regarding the role of CTCs in chemoresistance in metastatic breast cancer (MBC) patients. A search in Cochrane Library and MEDLINE databases was performed. A total of 125 articles were identified. The results of the final 12 eligible studies revealed that CTCs having stem cell features and those with mesenchymal features are aggressive subtypes of cells that survive chemotherapy, being responsible for chemoresistance and thus for disease progression in MBC patients. The hemodynamic shear stress, alongside dynamic changes among CTCs during the disease, is also an important disease progression factor.
Nutritional Intervention Contributes to the Improvement of Symptoms Related to Quality of Life in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Randomized Clinical Trial

During breast cancer treatment, worsening quality of life (QoL) and the presence of toxicities are common, but healthy eating practices are associated with better clinical results. Thus, this study aims to evaluate the effect of a nutritional intervention on QoL and on gastrointestinal and hematological toxicities resulting from chemotherapy in women with breast cancer. A randomized clinical trial was performed at the beginning of neoadjuvant chemotherapy treatment for women with breast cancer. All participants received nutritional advice on healthy eating practices, but only the intervention group (IG) received an individualized diet plan. The study enrolled 34 women, 19 in the IG and 15 in the control group (CG). During the study, the CG significantly presented a reduction (from 21.6 ± 5.9 kg to 18.8 ± 4.0 kg, p = 0.009) in handgrip strength (HGS), while the IG did not present changes in this variable. Regarding QoL, the IG preserved the role function during treatment and presented better results for nausea/vomiting and loss of appetite compared to the CG. In gastrointestinal and hematological toxicities, the IG had lower frequencies of leukopenia and abdominal pain. The nutritional intervention preserved the role function of QoL and HGS, reduced the occurrence of nausea/vomiting, loss of appetite and the frequency of leukopenia and abdominal pain.
Low-molecular-weight heparin versus unfractionated heparin in pediatric traumatic brain injury.

OBJECTIVE The incidence of venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) has increased significantly. The Eastern Association for the Surgery of Trauma recommends using low-molecular-weight heparin (LMWH) over unfractionated heparin (UH) in pediatric patients requiring VTE prophylaxis, although this strategy is unsupported by the literature. In this study, the authors compare the outcomes of pediatric TBI patients receiving LMWH versus UH. METHODS The authors performed a 4-year (2014-2017) analysis of the pediatric American College of Surgeons Trauma Quality Improvement Program. All trauma patients (age ≤ 18 years) with TBI requiring thromboprophylaxis with UH or LMWH were potentially eligible for inclusion. Patients who had been transferred, had died in the emergency department, or had penetrating trauma were excluded. Patients were stratified into either the LMWH or the UH group on the basis of the prophylaxis they had received. Patients were matched on the basis of demographics, injury characteristics, vital signs, and transfusion requirements using propensity score matching (PSM). The study endpoints were VTE, death, and craniotomy after initiation of prophylaxis. Univariate analysis was performed after PSM to compare outcomes. RESULTS A total of 2479 patients met the inclusion criteria (mean age 15.5 ± 3.7 years and 32.0% female), of which 1570 (63.3%) had received LMWH and 909 (36.7%) had received UH. Before PSM, patients receiving UH were younger, had a lower Glasgow Coma Scale score, and had a higher Injury Severity Score. Patients treated in pediatric hospitals were more likely to receive UH (12.9% vs 9.0%, p < 0.001) than patients treated in adult hospitals. Matched patients receiving UH had a higher incidence of VTE (5.1% vs 2.9%, p = 0.03). CONCLUSIONS LMWH prophylaxis in pediatric TBI appears to be more effective than UH in preventing VTE. Large, multicenter prospective studies are warranted to confirm the superiority of LMWH over UH in pediatric patients with TBI. Moreover, outcomes of VTE prophylaxis in the very young remain understudied; therefore, dedicated studies to evaluate this population are needed.
Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement.

OBJECTIVES To describe the processes used to update the PRISMA 2009 statement for reporting systematic reviews, present results of a survey conducted to inform the update, summarise decisions made at the PRISMA update meeting, and describe and justify changes made to the guideline. METHODS We reviewed 60 documents with reporting guidance for systematic reviews to generate suggested modifications to the PRISMA 2009 statement. We invited 220 systematic review methodologists and journal editors to complete a survey about the suggested modifications. The results of these projects were discussed at a 21-member in-person meeting. Following the meeting, we drafted the PRISMA 2020 statement and refined it based on feedback from co-authors and a convenience sample of 15 systematic reviewers. RESULTS The review of 60 documents revealed that all topics addressed by the PRISMA 2009 statement could be modified. Of the 110 survey respondents, more than 66% recommended keeping six of the original checklist items as they were and modifying 15 of them using wording suggested by us. Attendees at the in-person meeting supported the revised wording for several items but suggested rewording for most to enhance clarity, and further refinements were made over six drafts of the guideline. CONCLUSIONS The PRISMA 2020 statement consists of updated reporting guidance for systematic reviews. We hope that providing this detailed description of the development process will enhance the acceptance and uptake of the guideline and assist those developing and updating future reporting guidelines.
Enterotoxin Gene Distribution and Genotypes of Bacillus cereus sensu lato Isolated from Cassava Starch

Bacillus cereus is a human pathogenic bacterium found in foods with the potential to cause emesis and diarrhea. This study estimated the presence, toxigenic and genomic diversity of B. cereus s.l. obtained from cassava starch samples collected in bakeries and powdered food companies in Medellín (Colombia). Bacillus cereus s.l. was found in 43 of 75 (57%) cassava starch samples and 98 isolates were obtained. The nheABC, hblCDAB, cytK2, entFM and cesB toxin genes were detected by multiplex PCR and the most frequent operon was nheABC, whereas cesB gene was not found. Twelve toxigenic profiles were determined by the detection of toxin genes, and the most frequent profiles harbored all enterotoxin genes. A broad genomic diversity was detected according to GTG5-PCR fingerprinting results with 76 B. cereus s.l. grouped in sixteen clusters and the 22 isolates clustering separately. No relationship was observed between genomic background and toxigenic profiles. In general, the results showed a high genomic and enterotoxigenic diversity in B. cereus s.l. found in cassava starch. These results should incentive future studies to understand the distribution of B. cereus s.l. isolated on raw materials in comparison with finished products.
Platinum dissolution and tissue response following long-term electrical stimulation at high charge densities

Objective. Established guidelines for safe levels of electrical stimulation for neural prostheses are based on a limited range of the stimulus parameters used clinically. Recent studies have reported particulate platinum (Pt) associated with long-term clinical use of these devices, highlighting the need for more carefully defined safety limits. We previously reported no adverse effects of Pt corrosion products in the cochleae of guinea pigs following 4 weeks of electrical stimulation using charge densities far greater than the published safe limits for cochlear implants. The present study examines the histopathological effects of Pt within the cochlea following continuous stimulation at a charge density well above the defined safe limits for periods up to 6 months. Approach. Six cats were bilaterally implanted with Pt electrode arrays and unilaterally stimulated using charge balanced current pulses at a charge density of 267 μC cm−2 phase−1 using a tripolar electrode configuration. Electrochemical measurements were made throughout the implant duration and evoked potentials recorded at the outset and on completion of the stimulation program. Cochleae were examined histologically for particulate Pt, tissue response, and auditory nerve survival; electrodes were examined for surface corrosion; and cochlea, brain, kidney, and liver tissue analysed for trace levels of Pt. Main results. Chronic stimulation resulted in both a significant increase in tissue response and particulate Pt within the tissue capsule surrounding the electrode array compared with implanted, unstimulated control cochleae. Importantly, there was no stimulus-induced loss of auditory neurons (ANs) or increase in evoked potential thresholds. Stimulated electrodes were significantly more corroded compared with unstimulated electrodes. Trace analysis revealed Pt in both stimulated and control cochleae although significantly greater levels were detected within stimulated cochleae. There was no evidence of Pt in brain or liver; however, trace levels of Pt were recorded in the kidneys of two animals. Finally, increased charge storage capacity and charge injection limit reflected the more extensive electrode corrosion associated with stimulated electrodes. Significance. Long-term electrical stimulation of Pt electrodes at a charge density well above existing safety limits and nearly an order of magnitude higher than levels used clinically, does not adversely affect the AN population or reduce neural function, despite a stimulus-induced tissue response and the accumulation of Pt corrosion product. The mechanism resulting in Pt within the unstimulated cochlea is unclear, while the level of Pt observed systemically following stimulation at these very high charge densities does not appear to be of clinical significance.
A Molecular Tetrahedral Cobalt–Seleno-Based Complex as an Efficient Electrocatalyst for Water Splitting

The cobalt–seleno-based coordination complex, [Co{(SePiPr2)2N}2], is reported with respect to its catalytic activity in oxygen evolution and hydrogen evolution reactions (OER and HER, respectively) in alkaline solutions. An overpotential of 320 and 630 mV was required to achieve 10 mA cm−2 for OER and HER, respectively. The overpotential for OER of this CoSe4-containing complex is one of the lowest that has been observed until now for molecular cobalt(II) systems, under the reported conditions. In addition, this cobalt–seleno-based complex exhibits a high mass activity (14.15 A g−1) and a much higher turn-over frequency (TOF) value (0.032 s−1) at an overpotential of 300 mV. These observations confirm analogous ones already reported in the literature pertaining to the potential of molecular cobalt–seleno systems as efficient OER electrocatalysts.
Serum levels of anti-PspA and anti-PspC IgG decrease with age and do not correlate with susceptibility to experimental human pneumococcal colonization

Older adults are at increased risk of pneumococcal disease. This work aims to evaluate whether there is any decrease in serum IgG against variants of the antigens Pneumococcal surface protein A (PspA) and Pneumococcal surface protein C (PspC) in healthy adults with increasing age. Levels of IgG against PspA and PspC variants were determined by ELISA in serum samples comparing volunteers 18–30 years of age with volunteers who were 50–70+ before and after an experimental pneumococcal colonization challenge. The serotype 6B strain used in the challenge belongs to a minor group of pneumococcal isolates expressing two PspC variants. There was a decrease in levels of IgG with increasing age for the most common PspA variants and for all PspC variants analyzed. No correlation was found between basal levels of IgG against these antigens and protection against colonization. There was an increase in levels of IgG against PspA variants that are more cross-reactive with the variant expressed by the challenge strain post challenge in younger individuals who became colonized. Since the challenge strain used in our study expresses two different PspC variants, an increase in serum IgG against all PspC variants tested was observed in younger individuals who became colonized. For some of the antigen variants tested, a decrease in serum IgG was observed in young volunteers who were challenged but did not become colonized. Serum IgG antibodies against PspA and PspC variants thus decrease with age in healthy adults, but there is no correlation between levels of IgG against these antigens and protection against human experimental colonization. Though no correlation between naturally induced serum IgG antibodies against PspA and PspC and protection against colonization was observed, these results do not rule out the protective potential of these antigens as vaccines against pneumococcal infections.
Maternal Adherence to the Mediterranean Diet during Pregnancy: A Review of Commonly Used a priori Indexes

Currently, many a priori indexes are being used to assess maternal adherence to the Mediterranean diet (MD) during pregnancy but each with different components, cut-off points, and scoring systems. This narrative review aimed to identify all observational studies utilizing a priori indexes to assess maternal adherence to the MD during pregnancy. A systematic search was conducted in Pubmed until 1 July 2020. Among the 27 studies included, eight different a priori indexes were identified. Studies included a range of 5 to 13 dietary components in their indexes. Only three dietary components—vegetables, fruits, and fish—were common among all indexes. Dairy and alcohol were the only two components modified for pregnancy. All but one study either excluded alcohol from their index or reversed its scoring to contribute to decreased adherence to the MD. Approximately half of the studies established cut-off points based on the distribution of the study population; the others utilized fixed criteria. This review emphasizes the incongruent definitions of the MD impairing effective comparison among studies relating to maternal or offspring health outcomes. Future research should carefully consider the heterogeneous definitions of the MD in a priori indexes and the relevance of incorporating pregnancy-specific nutritional requirements.
Binding of phosphorothioate oligonucleotides with RNase H1 can cause conformational changes in the protein and alter the interactions of RNase H1 with other proteins

Abstract We recently found that toxic PS-ASOs can cause P54nrb and PSF nucleolar mislocalization in an RNase H1-dependent manner. To better understand the underlying mechanisms of these observations, here we utilize different biochemical approaches to demonstrate that PS-ASO binding can alter the conformations of the bound proteins, as illustrated using recombinant RNase H1, P54nrb, PSF proteins and various isolated domains. While, in general, binding of PS-ASOs or ASO/RNA duplexes stabilizes the conformations of these proteins, PS-ASO binding may also cause the unfolding of RNase H1, including both the hybrid binding domain and the catalytic domain. The extent of conformational change correlates with the binding affinity of PS-ASOs to the proteins. Consequently, PS-ASO binding to RNase H1 induces the interaction of RNase H1 with P54nrb or PSF in a 2′-modification and sequence dependent manner, and toxic PS-ASOs tend to induce more interactions than non-toxic PS-ASOs. PS-ASO binding also enhances the interaction between P54nrb and PSF. However, the interaction between RNase H1 and P32 protein can be disrupted upon binding of PS-ASOs. Together, these results suggest that stronger binding of PS-ASOs can cause greater conformational changes of the bound proteins, subsequently affecting protein–protein interactions. These observations thus provide deeper understanding of the molecular basis of PS-ASO-induced protein mislocalization or degradation observed in cells and advance our understanding of why some PS-ASOs are cytotoxic.
Nipple Sparing Mastectomy as a Risk-Reducing Procedure for BRCA-Mutated Patients

Growing numbers of asymptomatic women who become aware of carrying a breast cancer gene mutation (BRCA) mutation are choosing to undergo risk-reducing bilateral mastectomies with immediate breast reconstruction. We reviewed the literature with the aim of assessing the oncological safety of nipple-sparing mastectomy (NSM) as a risk-reduction procedure in BRCA-mutated patients. Nine studies reporting on the incidence of primary breast cancer post NSM in asymptomatic BRCA mutated patients undergoing risk-reducing bilateral procedures met the inclusion criteria. NSM appears to be a safe option for BRCA mutation carriers from an oncological point of view, with low reported rates of new breast cancers, low rates of postoperative complications, and high levels of satisfaction and postoperative quality of life. However, larger multi-institutional studies with longer follow-up are needed to establish this procedure as the best surgical option in this setting.
A unifying theory explaining venous sinus stenosis and recurrent stenosis following venous sinus stenting in patients with idiopathic intracranial hypertension

INTRODUCTION Idiopathic intracranial hypertension (IIH), or perhaps more accurately chronic intracranial venous hypertension syndrome (CIVHS), is a disabling condition often resulting in severe pressure headaches, visual symptoms, and tinnitus. In the last decade, venous sinus stenting (VSS) has emerged as a safe and effective treatment for patients with IIH with associated venous sinus stenosis and a documented transstenosis pressure gradient (TSPG). While metaanalyses of small retrospective series have demonstrated low rates of retreatment with high rates of headache and visual improvement, some recent studies have revealed that many patients (as high as 60%) develop symptom recurrence after VSS. There are very few published articles that provide neurointerventionists with recommendations regarding the selection and treatment of IIH patients and essentially no evidencebased recommendations are available regarding the specifics of stent construct lengths or sizes. Further, questions remain about the pathophysiologic mechanism at play and why recurrent stenosis develops. Experience gained from a highvolume VSS practice has provided important insights into these phenomena. Herein I propose a unifying theory that explains the pathophysiology of de novo and recurrent venous sinus stenosis in IIH patients, with attention given to how this may impact stent construct size and length.
Functional Analysis of Immune Signature Genes in Th1* Memory Cells Links ISOC1 and Pyrimidine Metabolism to IFN-γ and IL-17 Production

Key Points Functional analysis of Th1* immune signature genes uncovers novel regulators of IFN-γ and IL-17. Loss of ISOC1 impairs CD4+ T cell pyrimidine metabolism, bioenergetics, and cytokine production. CCR6+CXCR3+CCR4−CD4+ memory T cells, termed Th1*, are important for long-term immunity to Mycobacterium tuberculosis and the pathogenesis of autoimmune diseases. Th1* cells express a unique set of lineage-specific transcription factors characteristic of both Th1 and Th17 cells and display distinct gene expression profiles compared with other CD4+ T cell subsets. To examine molecules and signaling pathways important for the effector function of Th1* cells, we performed loss-of-function screening of genes selectively enriched in the Th1* subset. The genetic screen yielded candidates whose depletion significantly impaired TCR-induced IFN-γ production. These included genes previously linked to IFN-γ or M. tuberculosis susceptibility and novel candidates, such as ISOC1, encoding a metabolic enzyme of unknown function in mammalian cells. ISOC1-depleted T cells, which produced less IFN-γ and IL-17, displayed defects in oxidative phosphorylation and glycolysis and impairment of pyrimidine metabolic pathway. Supplementation with extracellular pyrimidines rescued both bioenergetics and IFN-γ production in ISOC1-deficient T cells, indicating that pyrimidine metabolism is a key driver of effector functions in CD4+ T cells and Th1* cells. Results provide new insights into the immune-stimulatory function of ISOC1 as well as the particular metabolic requirements of human memory T cells, providing a novel resource for understanding long-term T cell–driven responses.
Effect of Impurity Segregation on Crystal Morphology of Y-Bar Synthetic Quartz

The effects of Al and H impurities on the crystal morphology of Y-bar synthetic quartz were studied. The growth velocities perpendicular to the Y-axis were evaluated in relation to the Al and H impurity segregations on the growth interfaces. It was found that the -X-growth region has the highest H content and shows the lowest growth velocity, due to the effect of H2O adsorbed on the growth interface in hydrothermal solution. Therefore, the -X-face, (1̄1̄20), always becomes larger in size. Al has a selective effect on the (112̄2) and (1̄1̄22̄) faces to suppress the growth velocities and thus is important for crystal morphology. The growth velocities perpendicular to these faces, however, are controllable by the Al impurity content in the nutrient.
Forced convective boiling in vertical tubes for saturated pure components and binary mixtures

Over 1000 sets of data for forced convective boiling of distilled water, ethylene glycol and aqueous mixtures of ethylene glycol are reported. Most of these data were taken in the annular flow regime. These data indicate a previously unrecognized Prandtl number effect on the boiling heat transfer for both pure components and mixtures. A significant reduction in the heat transfer coefficient is observed for mixtures attributable to mass transfer effects. An expression is developed which accounts for both of these effects and correlates the experimental data to within a mean deviation of 14.9%. This correlation reduces to the standard Chen correlation for pure fluids with Prandtl numbers close to unity.
Wind and Stream Flow Induced Reaeration

Reaeration in combined wind/stream driven flows was experimentally studied in a laboratory wind-water tunnel. Wind velocities, stream flow properties, and oxygen transfer rates were measured under a variety of cocurrent and countercurrent flow conditions. For pure open channel flows and pure wind-driven flows, respectively, the results of oxygen transfer measurement can be scaled by the simple forcing parameters and show good agreement with other laboratory studies. For wind/stream combined flows, the transfer velocity depends on the stream flow condition and wind shear velocity. Based on the magnitude of the bottom-shear induced transfer and the wind-shear induced transfer velocity, a criterion was proposed to determine the dominant mechanism for gas transfer in combined wind/stream driven flows. A simple additive model is developed for the reaeration coefficient in combined wind and stream flow-influenced environments. Also, the effects of tidal flow on reaeration in tidal estuaries are briefly discussed.