Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep Brain Stimulation for Treatment-Resistant Depression: Towards a More Personalized Treatment Approach

Major depressive disorder (MDD) affects approximately 4.4% of the world’s population. One third of MDD patients do not respond to routine psychotherapeutic and pharmacotherapeutic treatment and are said to suffer from treatment-resistant depression (TRD). Deep brain stimulation (DBS) is increasingly being investigated as a treatment modality for TRD. Although early case studies showed promising results of DBS, open-label trials and placebo-controlled studies have reported inconsistent outcomes. This has raised discussion about the correct interpretation of trial results as well as the criteria for patient selection, the choice of stimulation target, and the optimal stimulation parameters. In this narrative review, we summarize recent studies of the effectiveness of DBS in TRD and address the relation between the targeted brain structures and clinical outcomes. Elaborating upon that, we hypothesize that the effectiveness of DBS in TRD can be increased by a more personalized and symptom-based approach. This may be achieved by using resting-state connectivity mapping for neurophysiological subtyping of TRD, by using individualized tractography to help decisions about stimulation target and electrode placement, and by using a more detailed registration of symptomatic improvements during DBS, for instance by using ‘experience sampling’ methods.
Post-traumatic stress disorder: A differential diagnostic consideration for COVID-19 survivors

Abstract Objective: SARS-CoV-2 infection and its oft-associated illness COVID-19 may lead to neuropsychological deficits, either through direct mechanisms (i.e., neurovirulance) or indirect mechanisms, most notably complications caused by the virus (e.g., stroke) or medical procedures (e.g., intubation). The history of past human coronavirus outbreaks resulting in similar health emergencies suggests there will be a substantial prevalence of post-traumatic stress disorder (PTSD) among COVID-19 survivors. To prepare neuropsychologists for the difficult task of differentiating PTSD-related from neuropathology-related deficits in the oncoming wave of COVID-19 survivors, we integrate research across a spectrum of related areas. Methods: Several areas of literature were reviewed: psychiatric, neurologic, and neuropathological outcomes of SARS and MERS patients; neurological outcomes in COVID-19 survivors; PTSD associated with procedures common to COVID-19 patients; and differentiating neuropsychological deficits due to PTSD from those due to acquired brain injuries in other patient groups. Conclusions: Heightened risk of PTSD occurred in MERS and SARS survivors. While data concerning COVID-19 is lacking, PTSD is known to occur in patient groups who undergo similar hospital courses, including ICU survivors, patients who are intubated and mechanically ventilated, and those that experience delirium. Research with patients who develop PTSD in the context of mild traumatic brain injury further suggests that PTSD may account for some or all of a patient’s subjective cognitive complaints and neuropsychological test performance. Recommendations are provided for assessing PTSD in the context of COVID-19.
Chemotherapy and Survival in Patients with Primary High-Grade Extremity and Trunk Soft Tissue Sarcoma

The use of upfront chemotherapy for primary localized soft tissue sarcoma (STS) of the extremity and trunk is debated. It remains unclear if chemotherapy adds clinical benefit, which patients are likely to benefit, and whether the timing of therapy affects outcomes. We used the National Cancer Database (NCDB) to examine the association between overall survival (OS) and chemotherapy in 5436 patients with the five most common subtypes of STS with primary disease localized to the extremity or trunk, mirroring the patient population of a modern phase 3 clinical trial of neoadjuvant chemotherapy. We then examined associations between timing of multi-agent chemotherapy (neoadjuvant or adjuvant) and OS. We used a Cox proportional hazards model and propensity score matching (PSM) to account for covariates including demographic, patient, clinical, treatment, and facility factors. In the overall cohort, we observed no association between multi-agent chemotherapy or its timing and improved OS. Multi-agent chemotherapy was associated with improved OS in several subgroups, including patients with larger tumors (>5 cm), those treated at high-volume centers, or those who received radiation. We also identified an OS benefit to multi-agent chemotherapy among the elderly (>70 years) and African American patients. Multi-agent chemotherapy was associated with improved survival for patients with tumors >5 cm, who receive radiation, or who receive care at high-volume centers. Neither younger age nor chemotherapy timing was associated with better outcomes. These ‘real-world’ findings align with recent randomized trial data supporting the use of multi-agent chemotherapy in high-risk patients with localized STS.
The efficacy and safety of osimertinib in treating nonsmall cell lung cancer

Supplemental Digital Content is available in the text Abstract Background: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the primary treatment in treating with EGFR mutant nonsmall cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of the third-generation EGFR-TKI, osimertinib, and summarize the risk factors associating with outcome after osimertinib treatment. Method: The Ovid Medline, Embase, Cochrane Library, and Pubmed were systematically searched due to December 10, 2019. All the studies that mentioned the overall survival (OS), progression-free survival (PFS), treatment response, and adverse events (AEs) of osimertinib were involved in our study. Hazard ratio (HR) with 95% confidence intervals was used for comparing OS and PFS. Result: A total of 47 studies were included in the systematic review, of which 14 studies were used to compare the efficacy between osimertinib and other EGFR-TKI or chemotherapy. Patients treating with osimertinib favors a higher OS and PFS in all the patients (HR = 0.56 and 0.38, P < .001, respectively), and in subgroup analysis, compared with other treatments. Median 55% T790 mutant NSCLC patients might experience partial response, and 25% of patients remained as stable disease. The incidence of severe AE ranged from 0% to 5%, and the most common severe AE was pneumonia (3%). Patients with the T858R mutation may have a better OS than Del 19 mutation (HR = 0.55, P = .037), while patients who have a smoking history may have a higher risk of progression than never-smoker patients (HR = 1.47, P = .028). Conclusion: Osimertinib has an impressive antitumor activity compared with prior EGFR-TKI and chemotherapy with an acceptable response and tolerable AEs. EGFR mutation type and smoking status were the risk factors for mortality and progression in NSCLC patients.
Laboratory-Based Surveillance of Clostridium difficile Infection in Australian Health Care and Community Settings, 2013 to 2018

In the early 2000s, a binary toxin (CDT)-producing strain of Clostridium difficile, ribotype 027 (RT027), caused extensive outbreaks of diarrheal disease in North America and Europe. This strain has not become established in Australia, and there is a markedly different repertoire of circulating strains there compared to other regions of the world. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is a nationwide longitudinal surveillance study of C. difficile infection (CDI) in Australia. ABSTRACT In the early 2000s, a binary toxin (CDT)-producing strain of Clostridium difficile, ribotype 027 (RT027), caused extensive outbreaks of diarrheal disease in North America and Europe. This strain has not become established in Australia, and there is a markedly different repertoire of circulating strains there compared to other regions of the world. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is a nationwide longitudinal surveillance study of C. difficile infection (CDI) in Australia. Here, we describe the molecular epidemiology of CDI in Australian health care and community settings over the first 5 years of the study, 2013 to 2018. Between 2013 and 2018, 10 diagnostic microbiology laboratories from five states in Australia participated in the CDARS study. From each of five states, one private (representing community) and one public (representing hospitals) laboratory submitted isolates of C. difficile or PCR-positive stool samples during two collection periods per year, February-March (summer/autumn) and August-September (winter/spring). C. difficile was characterized by toxin gene profiling and ribotyping. A total of 1,523 isolates of C. difficile were studied. PCR ribotyping yielded 203 different RTs, the most prevalent being RT014/020 (n = 449; 29.5%). The epidemic CDT+ RT027 (n = 2) and RT078 (n = 6), and the recently described RT251 (n = 10) and RT244 (n = 6) were not common, while RT126 (n = 17) was the most prevalent CDT+ type. A heterogeneous C. difficile population was identified. C. difficile RT014/020 was the most prevalent type found in humans with CDI. Continued surveillance of CDI in Australia remains critical for the detection of emerging strain lineages.
Health Technology Assessment Report on Vagus Nerve Stimulation in Drug-Resistant Epilepsy

Background: Vagus nerve stimulation (VNS) is a palliative treatment for medical intractable epileptic syndromes not eligible for resective surgery. Health technology assessment (HTA) represents a modern approach to the analysis of technologies used for healthcare. The purpose of this study is to assess the clinical, organizational, financial, and economic impact of VNS therapy in drug-resistant epilepsies and to establish the congruity between costs incurred and health service reimbursement. Methods: The present study used an HTA approach. It is based on an extensive detailed bibliographic search on databases (Medline, Pubmed, Embase and Cochrane, sites of scientific societies and institutional sites). The HTA study includes the following issues: (a) social impact and costs of the disease; (b) VNS eligibility and clinical results; (c) quality of life (QoL) after VNS therapy; (d) economic impact and productivity regained after VNS; and (e) costs of VNS. Results: Literature data indicate VNS as an effective treatment with a potential positive impact on social aspects and on quality of life. The diagnosis-related group (DRG) financing, both on national and regional levels, does not cover the cost of the medical device. There was an evident insufficient coverage of the DRG compared to the full cost of implanting the device. Conclusions: VNS is a palliative treatment for reducing seizure frequency and intensity. Despite its economic cost, VNS should improve patients’ quality of life and reduce care needs.
To tele- or not to telehealth? Ongoing COVID-19 challenges for private psychiatry in Australia

Objectives: Following a very rapid and significant uptake of metropolitan telepsychiatry in private practice in Australia during COVID-19, practical questions remain: How long should psychiatrists continue telepsychiatry? Are there benefits of continuing: reduced COVID-19 risks to patient and psychiatrist, and flexibility of appointments? Will the Medicare Benefits Schedule (MBS) telehealth items be retained? How does metropolitan telepsychiatry fit into the overall mix of public and private services? This is an important debate. Conclusions: Private psychiatrists may continue to offer the majority of care, where practical, via telepsychiatry to reduce COVID-19 exposure risks, as well as allow for the realities of practice management for pandemic public health measures. However, consideration has to be given to the potential drawbacks for patients with sight, hearing and illness-related disabilities or risks, when in-person consultation is required. There are also risks: some patients may not benefit from telepsychiatry due to the nature of their illness, and will patients feel rapport is lost? However, the retention of COVID-19 MBS telehealth items is needed for ongoing flexible and comprehensive private practice psychiatry.
Analysis of complete genomes of PCV2 in pigs with and without PMWS

According to the published genomic sequences of PCV2,a pair of specific primers was designed to amplify the complete genome of PCV2.With this PCR assay,four PCV2 complete gene fragments were amplified from pigs with PMWS,and seven were amplified from the tissues of healthy pigs.The fragments were cloned into pMD18-T vector and eleven recombinant plasmids were obtained,and named SDPCV,HBPCV,AHPCV,GSPCV,DZPCV1,DZPCV2,DZPCV3,NJPCV,BJPCV,BYPCV,QZPCV,respectivecy.Then the complete genomes of PCV2 isolates were determined.The results showed that the genomes of BJPCV and GSPCV isolates were 1 768 bp in length,and the others were 1 767 bp.The eleven sequences were compared with other fifteen PCV2 isolates from GenBank.The results indicated that the homology of complete genome sequence,ORF2 and the amino acid sequence deduced from ORF2 of PCV2 isolated from healthy pigs was slightly higher than that of the virus isolated from diseased pigs,but no remarkable difference in terms of ORF1 and ORF3.Phylogenetic tree analysis revealed that DZPCV3 in the present study was distantly related to the other ten PCV isolates,but was closely related to the Shandong isolates AY556473.And the other ten PCV isolates were close to each other,and they were closely related to a France isolates.The results showed there was no significant difference between the PCV2 in pigs with and without PMWS.
Olfactory dysfunction in patients after recovering from COVID-19

Abstract Background Smell and taste disorders occur in COVID-19 with a high prevalence, but little is known about the duration of the symptoms. In particular, studies using validated olfactory tests are very rare to date. Aims/Objectives The aim of this study was to determine the olfactory function of COVID-19 recoveries by a detailed olfactory test. Methods 91 patients with PCR-confirmed, past COVID-19 disease were included. Olfactory history was taken using a questionnaire. Olfactory function was evaluated with the sniffin' sticks test, tasting function with taste sprays. Results 80 patients had experienced sudden olfactory loss during the course of disease and at the time of testing, 33 patients subjectively still had an impaired olfactory sense. Around 8 weeks had passed since the onset of symptoms. 45.1% of the tested individuals were still hyposmic according to the olfactory test while 53.8% showed an olfactory performance within the normal range. Patients’ self-assessment correlated poorly with the measured olfactory performance. Conclusions and significance Half of the patients with an olfactory loss as a symptom of COVID-19 still have olfactory impairments after two months, although not all of these patients subjectively notice a restriction. Long-term measurements must confirm whether all affected patients will make full recovery.
Cats and dogs: Best friends or deadly enemies? What the owners of cats and dogs living in the same household think about their relationship with people and other pets

Although popular culture describes them as mortal enemies, more and more often, dogs and cats live under the same roof. Does this make them best friends? Can sharing the same social and physical environment make them similar? This study compares the approaches of dogs and cats living in the same household have towards humans and other pets as perceived by the owner. Questionnaires collected from 1270 people owning both dog(s) and cat(s) were analysed. Most dogs and cats living together are playful with familiar humans (76.2%) but dogs have a more sociable approach towards strangers and conspecifics than cats (P<0.001). Moreover, the percentage of dogs that have a playful relationship with the owner (84.0%) was higher than cats (49.2%; P<0.001). Dogs and cats living together eat in different places and show different mutual interactions: more dogs lick the cat (42.8%) and more cats ignore the dog (41.8%) than vice versa (P<0.001). However, most dogs and cats sleep at least occasionally (68.5%) and play together (62.4%; P<0.001). Although some body postures, such as the tail’s position, are interpreted differently by the two species, the greater proportions of dogs and cats show a relaxed response to several kinds of approaches of their roommate. Our questionnaire confirms the common beliefs about the sociability of the dog and the privacy of the cat, but this does not result in continuous internal struggles. Most cohabitations are peaceful. Moreover, it is true that they speak different languages, but they seem to understand each other well and interpret each other's approaches in the right way. Thus, aspiring owners should not blindly believe popular assumptions, but both knowledge and respect for species-specific pet behaviours are essential to establish a balance in the household.
The effect of dietary methionine on growth, antioxidant capacity, innate immune response and disease resistance of juvenile yellow catfish (Pelteobagrus fulvidraco)

An 11-week feeding trial was conducted to evaluate the effect of dietary methionine on the growth, antioxidant status, innate immune response and disease resistance to Aeromonas hydrophila of juvenile yellow catfish. Six isonitrogenous and isolipidic practical diets were formulated to contain different graded methionine levels ranging from 6.1 to 16.4 g kg−1 of dry weight. The results indicated that growth performance and feed utilization were significantly influenced by the dietary methionine levels; fish fed the diet containing 6.1 g kg−1 methionine level had lower specific growth rate, percentage weight gain (PWG), feed efficiency and protein efficiency ratio than those fed the other diets (P < 0.05). Fish fed the diet containing 16.4 g kg−1 methionine level had lowest protein contents in whole body and muscle among all treatments. Triacylglycerols, cholesterol, aspartate aminotransferase, alanine aminotransferase and haemoglobin (Hb) in plasma or whole blood were significantly affected by dietary methionine levels. Fish fed the diet containing 6.1 g kg−1 methionine level had higher superoxide dismutase, glutathione peroxidase activities and malondialdehyde values than those fed other diets. Fish fed diets containing 9.7 and 11.8 g kg−1 methionine levels had higher lysozyme activity, total immune globulin, phagocytic activity and respiratory burst than those fed other diets. The lowest survival after A. hydrophila challenge was observed in fish fed a diet containing 6.1 g kg−1 methionine. Quadratic regression analysis of PWG against dietary methionine levels indicated that the optimal dietary methionine requirement for the maximum growth of juvenile yellow catfish was estimated to be 11.5 g kg−1 of the diet in the presence of 4.0 g kg−1 cystine (corresponding to 23.5 g kg−1 of dietary protein on a dry weight basis).
A 12-Week Multi-Modal Exercise Program: Feasibility of Combined Exercise and Simplified 8-Style Tai Chi Following Lung Cancer Surgery

Objective: To assess the feasibility, safety, and preliminary effect of a 12-week multi-modal rehabilitation program targeted at improving health-related quality of life and physical activity levels of patients with lung cancer following treatment. Methods: Patients with stage I to IIIA non-small cell lung cancer were included 6 to 12 weeks following completion of treatment. The intervention comprised of aerobic exercise (brisk walking), resistance training and 8-style Tai Chi. The 12-week program included 2 supervised center-based sessions per week of 90 minutes duration and home-based exercise. The primary outcomes were the feasibility and safety of the intervention. Secondary outcomes (assessed pre and post program) were physical and patient-reported outcomes. Results: Seventy-eight patients were approached during the 6-month recruitment period and 17 (22%) consented to the study. Eight participants (47%) met the definition of adherence to the program (attending at least 70% of supervised sessions). No serious adverse events occurred. A significant reduction in anxiety and depression was observed post-program. In addition, improvements in respiratory function, sleep quality, and some health-related quality of life domains were observed post-program. There were no significant differences in functional capacity or physical activity levels. Conclusion: This multi-modal exercise training program was safe, although the feasibility of the program in its current state is not supported given the low consent rate and low adherence to the intervention.
New iridoid glucosides from the roots of Rothmannia wittii (Craib) Bremek

Abstract Phytochemical investigation of the roots of Rothmannia wittii led to the isolation of three new iridoid glucosides, named rothmanniosides A–C (1–3), and nine known compounds (4–12). Their structures, including their absolute configurations, were elucidated by thorough analysis of mass spectrometric and NMR spectroscopic data, together with CD calculations. Compounds 4 and 11 are reported from the Rubiaceae family for the first time. Graphical Abstract
Tongxinluo attenuates oxygen-glucose-serum deprivation/restoration-induced endothelial barrier breakdown via peroxisome proliferator activated receptor-α/angiopoietin-like 4 pathway in high glucose-incubated human cardiac microvascular endothelial cells

Abstract Background: Traditional Chinese medicine Tongxinluo (TXL) has been widely used to treat coronary artery disease in China, since it could reduce myocardial infarct size and ischemia/reperfusion injury in both non-diabetic and diabetic conditions. It has been shown that TXL could regulate peroxisome proliferator activated receptor-α (PPAR-α), a positive modulator of angiopoietin-like 4 (Angptl4), in diabetic rats. Endothelial junction substructure components, such as VE-cadherin, are involved in the protection of reperfusion injury. Thus, we hypothesized cell-intrinsic and endothelial-specific Angptl4 mediated the protection of TXL on endothelial barrier under high glucose condition against ischemia/reperfusion-injury via PPAR-α pathway. Methods: Incubated with high glucose medium, the human cardiac microvascular endothelial cells (HCMECs) were then exposed to oxygen-glucose-serum deprivation (2 hours) and restoration (2 hours) stimulation, with or without TXL, insulin, or rhAngptl4 pretreatment. Results: TXL, insulin, and rhAngptl4 had similar protective effects on the endothelial barrier. TXL treatment reversed the endothelial barrier breakdown in HCMECs significantly as identified by decreasing endothelial permeability, upregulating the expression of JAM-A, VE-cadherin, and integrin-α5 and increasing the membrane location of VE-cadherin and integrin-α5, and these effects of TXL were as effective as insulin and rhAngptl4. However, Angptl4 knock-down with small interfering RNA (siRNA) interference and PPAR-α inhibitor MK886 partially abrogated these beneficial effects of TXL. Western blotting also revealed that similar with insulin, TXL upregulated the expression of Angptl4 in HCMECs, which could be inhibited by Angptl4 siRNA or MK886 exposure. TXL treatment increased PPAR-α activity, which could be diminished by MK886 but not by Angptl4 siRNA. Conclusion: These data suggest cell-intrinsic and endothelial-specific Angptl4 mediates the protection of TXL against endothelial barrier breakdown during oxygen-glucose-serum deprivation and restoration under high glucose condition partly via the PPAR-α/Angptl4 pathway.