Miracle-dz/UniFAR-FTUs huggingface dataset:
The insolvable problem; survival effect of lymphadenectomy in advanced stage ovarian cancer.

OBJECTIVES In this study, we aimed to evaluate the effect of systemic lymphadenectomy on overall and progression free survival in advanced stage of ovarian cancer. MATERIAL AND METHODS The data of ovarian cancer patients who had been admitted to our clinic between March 2008 and December 2019 were collected retrospectively. The patients who had received neo-adjuvant chemotherapy (NACT), those having undergone interval surgery, those who had non-epithelial ovarian cancer, those with residual tumour larger than 1 cm and those with stage I-IIA were excluded from the study. RESULTS A total of 241 patients with inclusion criteria were included in the study. While 169 patients (70.1%) had undergone systemic lymphadenectomy (SLND), 72 (29.9%) had not. Lymph node involvement was present in 105 out of 169 patients (62.1%) who had undergone SLND. There was no statistically significant difference between the groups in terms of SLND and lymph node involvement for both progression free survival (PFS) and overall survival (OS) (p = 0.577, p = 0.493, p = 0.481, p = 0.849 respectively). When subgroup analysis was performed according to the residual tumor amount, we could not find any statistically significant difference in both PFS and OS in terms of SLND and lymph node involvement in R0 (complete resection) group (p = 0.057, p = 0.917, p = 0.106 and p = 0.980 respectively). We found similar results for patients in the R1 (optimal resection) group. CONCLUSIONS It was found that performing systemic lymphadenectomy had no effect on both progressive and overal survival. It should be kept in mind that the increasing number of malignant lymph nodes removed could have a therapeutic effect in OS. Large numbers of randomized clinical trials are required to enlighten this debatable issue that has been continuing, particularly in the recent two decades.
Lack of immune response after mRNA vaccination to SARS‐CoV‐2 in a solid organ transplant patient

The recent approval and distribution of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) have been a major development in the fight against the current coronavirus disease 2019 (COVID‐19) pandemic. The first two vaccines approved in the United States, mRNA‐1273, and BNT162b2, are both messenger RNA (mRNA) based and highly effective in immunocompetent persons, but efficacy in patients on immunosuppressants has not been established. Additionally, data suggests these patients are less likely than immunocompetent people to develop neutralizing antibodies after COVID‐19 infection. Given the high risk of poor outcomes in organ transplant and immunosuppressed patients, effective vaccination is paramount in this group. We present the first reported case of a solid organ transplant patient who failed to achieve seroconversion after two doses of mRNA vaccine. This case has significant implications about how immunosuppressed patients should be counseled about SARS‐CoV‐2 vaccination and the protection provided. Physicians should remain clinically suspicious for infection with SARS‐CoV‐2 despite vaccination status in solid organ transplant patients.
Immunosuppressive therapy withdrawal after remission achievement in patients with lupus nephritis.

AIM Whether immunosuppressive therapy (IS) may be safely withdrawn in lupus nephritis (LN) is still unclear. We assessed rate and predictors of flare after IS withdrawal in patients with LN in remission. METHODS Patients with biopsy-proven LN treated with IS between 1980 and 2020 were considered. Remission was defined as normal serum creatinine, proteinuria <0.5 g/24h, inactive urine sediment, and no extra-renal SLE activity on stable immunosuppressive and/or antimalarial therapy and/or prednisone ≤5mg/day. IS discontinuation was defined as the complete withdrawal of immunosuppressants, flares according to SLEDAI Flare Index. Predictors of flare were analyzed by multivariate logistic regression analysis. RESULTS Among 513 SLE patients included in our database, 270 had LN. Of them, 238 underwent renal biopsy and were treated with ISs. Eighty-three patients (34.8%) discontinued IS, 46 ± 30 months after remission achievement. During a mean±SD follow-up of 116.5 ± 78 months, 19 patients (22.8%) developed a flare (8/19 renal) and were re-treated; 14/19 (73.7%) re-achieved remission after restarting therapy. Patients treated with IS therapy for at least three years after remission achievement had the lowest risk of relapse (OR 0.284, 95% CI 0.093-0.867, p= 0.023). At multivariate analysis, antimalarial maintenance therapy (OR 0.194, 95%CI 0.038-0.978, p= 0.047), age at IS discontinuation (OR 0.93, 95%CI 0.868-0.997, p= 0.040), remission duration >3 years before IS discontinuation (OR 0.231, 95%CI 0.058-0.920, p= 0.038) were protective against disease flares. CONCLUSIONS Withdrawal of IS is feasible in LN patients in remission for at least 3 years and on antimalarial therapy. Patients who experience flares can re-achieve remission with an appropriate treatment.
Cancer cells retrace a stepwise differentiation program during malignant progression.

Pancreatic Neuroendocrine Tumors (PanNETs) comprise two molecular subtypes, relatively benign islet tumors (IT) and invasive, metastasis-like primary (MLP) tumors. Hitherto, the origin of aggressive MLP tumors has been obscure. Herein, using multi-omics approaches, we revealed that MLP tumors arise from IT via dedifferentiation following a reverse trajectory along the developmental pathway of islet B-cells, which results in the acquisition of a progenitor-like molecular phenotype. Functionally, the microRNA-181cd cluster induces the IT-to-MLP transition by suppressing expression of the Meis2 transcription factor, leading to upregulation of a developmental transcription factor, Hmgb3. Notably, the IT-to-MLP transition constitutes a distinct step of tumorigenesis and is separable from the classical proliferation-associated hallmark, temporally preceding accelerated proliferation of cancer cells. Furthermore, PanNET patients with elevated HMGB3 expression and an MLP transcriptional signature are associated with higher-grade tumors and worse survival. Overall, our results unveil a new mechanism that modulates cancer cell plasticity to enable malignant progression.
Combined local delivery of tacrolimus and stem cells in hydrogel for enhancing peripheral nerve regeneration

The application of scaffold‐based stem cell transplantation to enhance peripheral nerve regeneration has great potential. Recently, the neuroregenerative potential of tacrolimus (a U.S. Food and Drug Administration‐approved immunosuppressant) has been explored. In this study, a fibrin gel‐based drug delivery system for sustained and localized tacrolimus release was combined with rat adipose‐derived mesenchymal stem cells (MSC) to investigate cell viability in vitro. Tacrolimus was encapsulated in poly(lactic‐co‐glycolic) acid (PLGA) microspheres and suspended in fibrin hydrogel, using concentrations of 0.01 and 100 ng/ml. Drug release over time was measured. MSCs were cultured in drug‐released media collected at various days to mimic systemic exposure. MSCs were combined with (i) hydrogel only, (ii) empty PLGA microspheres in the hydrogel, (iii) 0.01, and (iv) 100 ng/ml of tacrolimus PLGA microspheres in the hydrogel. Stem cell presence and viability were evaluated. A sustained release of 100 ng/ml tacrolimus microspheres was observed for up to 35 days. Stem cell presence was confirmed and cell viability was observed up to 7 days, with no significant differences between groups. This study suggests that combined delivery of 100 ng/ml tacrolimus and MSCs in fibrin hydrogel does not result in cytotoxic effects and could be used to enhance peripheral nerve regeneration.
Aerosol-generating behaviours in speech pathology clinical practice: A systematic literature review

Objective To evaluate the evidence of aerosol generation across tasks involved in voice and speech assessment and intervention, to inform better management and to reduce transmission risk of such diseases as COVID-19 in healthcare settings and the wider community. Design Systematic literature review. Data sources and eligibility Medline, Embase, Scopus, Web of Science, CINAHL, PubMed Central and grey literature through ProQuest, The Centre for Evidence-Based Medicine, COVID-Evidence and speech pathology national bodies were searched up until August 13th, 2020 for articles examining the aerosol-generating activities in clinical voice and speech assessment and intervention within speech pathology. Results Of the 8288 results found, 39 studies were included for data extraction and analysis. Included articles were classified into one of three categories: research studies, review articles or clinical guidelines. Data extraction followed appropriate protocols depending on the classification of each article (e.g. PRISMA for review articles). Articles were assessed for risk of bias and certainty of evidence using the GRADE system. Six behaviours were identified as aerosol generating. These were classified into three categories: vegetative acts (coughing, breathing), verbal communication activities of daily living (speaking, loud voicing), and performance-based tasks (singing, sustained phonation). Certainty of evidence ranged from very low to moderate with variation in research design and variables. Conclusions This body of literature helped to both identify and categorise the aerosol-generating behaviours involved in speech pathology clinical practice and confirm the low level of evidence throughout the speech pathology literature pertaining to aerosol generation. As many aerosol-generating behaviours are common human behaviours, these findings can be applied across healthcare and community settings. Systematic review registration Registration number CRD42020186902 with PROSPERO International Prospective Register for Systematic Reviews.
Population-Based Estimates of SARS-CoV-2 Seroprevalence in Houston, TX as of September 2020

Abstract Background In contrast to studies that relied on volunteers or convenience sampling, there are few population-based SARS-CoV-2 seroprevalence investigations and most were conducted early in the pandemic. The health department of the fourth largest city in the U.S. recognized that sound estimates of viral impact were needed to inform decision-making. Methods Adapting standardized disaster research methodology in September 2020, the city was divided into high and low strata based on RT-PCR positivity rates, and census block groups within each stratum were randomly selected with probability proportional to size, followed by random selection of households within each group. Using two immunoassays, the proportion of infected individuals was estimated for the city, as well as by positivity rate and by sociodemographic and other characteristics. The degree of under ascertainment of seroprevalence was estimated based on RT-PCR positive cases. Results Seroprevalence was estimated to be 14% with a near two-fold difference in areas with high (18%) versus low (10%) RT-PCR positivity rates and was four times higher compared to case-based surveillance data. Conclusions Seroprevalence was higher than previously reported and is greater than that estimated from RT-PCR data. Results will be used to inform public health decisions about testing, outreach, and vaccine rollout.
Mepolizumab improves sino-nasal symptoms and asthma control in severe eosinophilic asthma patients with chronic rhinosinusitis and nasal polyps: a 12-month real-life study

Background: Severe eosinophilic asthma is frequently associated to chronic rhinosinusitis and nasal polyposis (CRSwNP) that contribute to poor asthma control. Mepolizumab is an anti-IL-5 monoclonal antibody, approved for the treatment of severe eosinophilic asthma. A limited number of studies have assessed the efficacy of mepolizumab on CRSwNP in severe asthmatics. We aim to evaluate the efficacy of mepolizumab on sino-nasal symptoms, polyp growth and asthma control in severe eosinophilic asthma patients with CRSwNP in real life. Methods: In this study 44 severe eosinophilic asthma patients with CRSwNP were treated with mepolizumab (100 mg q4w) for 1 year. The following outcomes were assessed before (T0), after 6 (T6) and 12 months (T12) of treatment: sino/nasal outcome test (SNOT-22), Total Endoscopic Nasal Polyp Score (TENPS), %FEV1 (FEV1/FEV1 predicted) and Asthma control test (ACT). Blood eosinophil count, exhaled nitric oxide (FENO) and prednisone intake were measured. In a subgroup of patients, nasal cytology was performed before (T0), after 6 (T6) and after 12 months (T12) of treatment with mepolizumab. Results: We reported a significant reduction of SNOT-22 [from 51.5 ± 21.2 at baseline (T0) to 31.70 ± 17.36 at T6 and 29.7 ± 21.5 at T12 (T0–T12 p < 0.001)] and a decrease of TENPS (from 2.88 ± 3.07 to 1.70 ± 2.37 and 1.77 ± 2.56 at T0, T6 and T12, respectively, T0–T12 p = 0.99). A significant improvement of %FEV1, ACT and a decrease in blood eosinophils and mean prednisone intake were also reported. No statistically significant decreasing trend was measured for FENO. Nasal cytology findings suggest a significant reduction of eosinophil percentage following mepolizumab treatment (from 16.8 ± 7.2% to 3.6 ± 6.2% and 0.8 ± 2.4% at T0, T6 and T12 respectively, T0 to T12: p < 0.001). Conclusions: Mepolizumab improves sino-nasal and asthma symptoms and reduces polyp growth in patients with severe eosinophilic asthma and concomitant CRSwNP in real life. The reviews of this paper are available via the supplemental material section.
Early Coagulopathy in Pediatric Traumatic Brain Injury: A Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) Retrospective Study

Abstract BACKGROUND Although early coagulopathy increases mortality in adults with traumatic brain injury (TBI), less is known about pediatric TBI. OBJECTIVE To describe the prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet levels of children with moderate to severe TBI to identify predictors of early coagulopathy and study the association with clinical outcomes. METHODS Using the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) TBI retrospective cohort, we identified patients <16 yr old with a Glasgow Coma Scale (GCS) ≤13. We compared PT, APTT, platelets, and outcomes between children with isolated TBI and multiple trauma with TBI. We performed logistic regressions to identify predictors of early coagulopathy and study the association with mortality and poor functional outcomes. RESULTS Among 370 children analyzed, 53/370 (14.3%) died and 127/370 (34.3%) had poor functional outcomes. PT was commonly deranged in both isolated TBI (53/173, 30.6%) and multiple trauma (101/197, 51.3%). Predictors for early coagulopathy were young age (adjusted odds ratio [aOR] 0.94, 95% CI 0.88-0.99, P = .023), GCS < 8 (aOR 1.96, 95% CI 1.26-3.06, P = .003), and presence of multiple trauma (aOR 2.21, 95% confidence interval [CI] 1.37-3.60, P = .001). After adjusting for age, gender, GCS, multiple traumas, and presence of intracranial bleed, children with early coagulopathy were more likely to die (aOR 7.56, 95% CI 3.04-23.06, P < .001) and have poor functional outcomes (aOR 2.16, 95% CI 1.26-3.76, P = .006). CONCLUSION Early coagulopathy is common and independently associated with death and poor functional outcomes among children with TBI.
Incidence of postoperative endophthalmitis with and without use of intracameral moxifloxacin

Dear Editor, With modern operating rooms and advanced autoclave facilities, the reported incidence of postoperative endophthalmitis ranges from 0.01% to 0.367%, with incidence varying among different surgical procedures, various studies and different countries. [1‐3] Usage of intracameral (IC) antibiotics, at end of intraocular surgery as a prophylaxis to reduce occurrence of endophthalmitis, has been recommended by the American Society of Cataract and Refractive Surgery. [4] Small incision cataract surgery (SICS) is commonly done in India, especially in trust hospital as a low‐cost high‐volume strategy. We conducted a retrospective study over a period of 2 years to evaluate IC moxifloxacin as prophylaxis to reduce rate of endophthalmitis, in cases before and after initiation of IC moxifloxacin in a high‐volume surgical set‐up where SICS was done in all cases.
Ab Initio Modeling of MultiWall: A General Algorithm First Applied to Carbon Nanotubes

A general, versatile and automated computational algorithm to design any type of multiwall nanotubes of any chiralities is presented for the first time. It can be applied to rolling up surfaces obtained from cubic, hexagonal, and orthorhombic lattices. Full exploitation of the helical symmetry permits a drastic reduction of the computational cost and therefore opens to the study of realistic systems. As a test case, the structural, electronic, mechanical, and transport properties of multiwall carbon nanotubes (MWCNT) are calculated using a density functional theory approach, and results are compared with those of the corresponding layered (graphene-like) precursors. The interaction between layers has a general minimum for the inter-wall distance of ≈3.4 Å, in good agreement with experimental and computed optimal distances in graphene sheets. The metallic armchair and semiconductor zigzag MWCNT are almost isoenergetic and their stability increases as the number of walls increases. The vibrational fingerprint provides a reliable tool to identify the chirality and the thickness of the nanostructures. Finally, some promising thermoelectric features of the semiconductor MWCNT are reproduced and discussed.
Sex Differences in Acute Alcohol Sensitivity of Naïve and Alcohol Dependent Central Amygdala GABA Synapses.

AIMS Alcohol use disorder (AUD) is linked to hyperactivity of brain stress systems, leading to withdrawal states which drive relapse. AUD differs among the sexes, as men are more likely to have AUD than women, but women progress from casual use to binge and heavy alcohol use more quickly and are more likely to relapse into repetitive episodes of heavy drinking. In alcohol dependence animal models of AUD, the central amygdala (CeA) functions as a hub of stress and anxiety processing and gamma-Aminobutyric acid (GABA)ergic signaling within the CeA is involved in dependence-induced increases in alcohol consumption. We have shown dysregulation of CeA GABAergic synaptic signaling in alcohol dependence animal models, but previous studies have exclusively used males. METHODS Here, we used whole-cell patch clamp electrophysiology to examine basal CeA GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) and the effects of acute alcohol in both naïve and alcohol dependent rats of both sexes. RESULTS We found that sIPSC kinetics differ between females and males, as well as between naïve and alcohol-dependent animals, with naïve females having the fastest current kinetics. Additionally, we find differences in baseline current kinetics across estrous cycle stages. In contrast to the increase in sIPSC frequency routinely found in males, acute alcohol (11-88 mM) had no effect on sIPSCs in naïve females, however the highest concentration of alcohol increased sIPSC frequency in dependent females. CONCLUSION These results provide important insight into sex differences in CeA neuronal function and dysregulation with alcohol dependence and highlight the need for sex-specific considerations in the development of effective AUD treatment.
Lithium ions display weak interaction with amyloid-beta (Aβ) peptides and have minor effects on their aggregation

Alzheimer’s disease (AD) is an incurable disease and the main cause of age-related dementia worldwide, despite decades of research. Treatment of AD with lithium (Li) has showed promising results, but the underlying mechanism is unclear. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils. The plaques contain also metal ions of e.g. Cu, Fe, and Zn, and such ions are known to interact with Aβ peptides and modulate their aggregation and toxicity. The interactions between Aβ peptides and Li+ ions have however not been well investigated. Here, we use a range of biophysical techniques to characterize in vitro interactions between Aβ peptides and Li+ ions. We show that Li+ ions display weak and non-specific interactions with Aβ peptides, and have minor effects on Aβ aggregation. These results indicate that possible beneficial effects of Li on AD pathology are not likely caused by direct interactions between Aβ peptides and Li+ ions.
Chorionic villus sampling and preeclampsia & eclampsia: coincidence or not?

Abstract Objectives The purpose of the study is to investigate potential association of chorionic villus sampling (CVS) with subsequent development of preeclampsia (PE) and eclampsia (E). Study design The development of PE and E was compared between two groups as follows: 1- CVS group: women who underwent CVS (n = 228) and 2- Control group: maternal and gestational age matched women without invasive prenatal diagnostic procedure (n = 456). Main outcome measures were incidence of PE (mild, severe) and E. Results The incidence of PE and E was not significantly different between CVS and control groups. There was no significant difference regarding mild and severe PE development between the two groups. The incidence of early- and late-onset PE was similar in CVS and control groups. Conclusions CVS does not appear to increase the risk of PE and E. The spontaneous elevation of trophoblastic load in the maternal circulation rather than the iatrogenic elevation through CVS may contribute to the development of PE and E.
Performance, clinical effectiveness, and safety of immunoadsorption in a wide range of indications

Immunoadsorption is well known to selectively remove immunoglobulins and immune complexes from plasma and is applied in a variety of autoimmune diseases and for desensitization before, or at acute rejection after organ transplantation. Performance, safety, and clinical effectiveness of immunoadsorption were the aim of this study. This prospective, noninterventional, multicentre cohort study included patients treated with immunoadsorption (Immunosorba or GLOBAFFIN adsorbers) for any indication. Clinical effectiveness was assessed after termination of the patient's individual treatment schedule. Eighty‐one patients were included, 69 were treated with Immunosorba, 11 with GLOBAFFIN, one patient with both adsorbers. A majority of patients was treated for neurological indications, dilated cardiomyopathy, and before or after kidney or heart transplantation. Mean IgG reduction from pre‐ to post‐treatment was 69.9% ± 11.5% for Immunosorba and 74.1% ± 5.0% for GLOBAFFIN, respectively. The overall IgG reduction over a complete treatment block was 68%–93% with Immunosorba and 62%–90% with GLOBAFFIN depending on the duration of the overall treatment. After termination of the immunoadsorption therapy, an improvement of clinical status was observed in 63.0%, stabilization of symptoms in 29.6%, and a deterioration in 4.9% of patients. Changes in fibrinogen, thrombocytes, and albumin were mostly classified as noncritical. Overall, the treatments were well tolerated. Immunoadsorption in routine clinical practice with both GLOBAFFIN and Immunosorba has been safely performed, was well tolerated by patients, and effective in lowering immunoglobulins with an improvement or maintenance of clinical status, thus represents an additional therapeutic option for therapy refractory immune disorders.