Miracle-dz/UniFAR-FTUs huggingface dataset:
Antidepressant Use and the Risk of Mood Instability.

Dear Editor, Freitas C et al1 recently published a case report on a widely discussed topic in psychiatry, concerning the risk of manic switch with the use of antidepressants. This topic is of the utmost importance especially considering today’s widespread use of antidepressants in a wide range of medical conditions. Although the risk of switching with antidepressants is well established, its adverse effects in the management in other clinical conditions are often underestimated in psychiatry. At the core of this issue is the accurate diagnosis of depressive episodes. Today’s classification systems on mood disorders are largely based on a polarity dichotomy (unipolar versus bipolar). Frequently it is assumed that any depressive state is synonymous with the diagnosis of unipolar depression, overlooking subsyndromal signs of hypomanic or mixed depressive states. A previous history of treatment resistant depression, irritability, mood lability, mixed features in response to antidepressants is associated with a possible underlying bipolar diathesis.2 Indeed, some authors propose that up to half of supposedly unipolar depressive episodes presenting in clinical practice might be diagnosed as depressive mixed states if one takes into consideration criteria excluded from DSM 5 mixed features specifier (such as psychomotor agitation, distractibility, irritability, racing thoughts). 3,4 Radical thinkers go as far as proposing the apparently controversial view that depression is a consequence of manic states.3 According to this point of view, antidepressants are ineffective and harmful in the treatment of most depressive episodes presenting in clinical practice, and thus contribute to induce further mood instability in these patients. Indeed, most depressive states in clinical practice would involve mixed depressive states, affective temperaments (cyclothymia and hyperthymia) and classical bipolar depression.5 Misdiagnosis of soft bipolar spectrum disorders or temperamental dysregulations (such as cyclothymia) may lead to frustration amongst clinicians with patients failing to improve and apparently resisting to recommended pharmacological and psychological treatment. The mainstay treatment should include the slow discontinuation of antidepressants and the use of drugs with mood stabilizing properties (lithium, anticonvulsants and second-generation antipsychotics). 4,5 Current evidence would recommend against the use of antidepressant monotherapy in the treatment of bipolar spectrum depression. The key message is to be mindful of associated features and signs that depressive episodes (even in the absence of past mania or hypomania) might not be truly ‘unipolar’ (Table 1). This might help to prevent misdiagnosis and inappropriate treatment strategies with potential negative long-term prognostic implications (including increased suicide risk).
Reducing the Risk of Preterm Birth by Ambulatory Risk Factor Management.

BACKGROUND The preterm birth rate in Germany has remained unchanged at 8-9% since 2009. Preterm birth is the most common cause of neonatal morbidity and mortality. In the absence of a causal treatment, it is important to lower the risk of preterm birth by preventive measures in prenatal outpatient care. METHODS This review is based on pertinent publications from the years 2000-2019 that were retrieved by a selective search in PubMed. RESULTS The clinical risk factors for preterm birth-known mainly from retrospective cohort studies-include previous preterm birth (adjusted odds ratio [aOR]: 3.6), multiple pregnancy (relative risk [RR]: 7.7), nicotine consumption (aOR: 1.7), and a short uterine cervix, i.e., <25 mm in the second trimester (aOR: 6.9). In women with a short cervix, vaginally administered progesterone significantly lowers the preterm birth rate (22.5% vs. 14.1% for birth before 33 weeks of gestation, RR: 0.62; 95% confidence interval [0.47; 0.81]). Nicotine abstinence is associated with a lower pre- term birth rate as well (aOR: 0.91; [0.88; 0,.94]), while working more than 40 hours per week (aOR: 1.25; [1,.01; 1,.54]) and heavy lifting during pregnancy (hazard ratio [HR]: 1.43; [1.13; 1.80]) are associated with a higher preterm birth rate. Avoidance of physical exertion, or bed rest, in the face of impending preterm birth does not lower the preterm birth rate, but it does increase the risk of complications, such as thromboembolism. CONCLUSION The meticulous assessment and elimination of treatable risk factors at the outset of ambulatory prenatal care can help lower the preterm birth rate. Further velopment of causally directed treat- ments (e.g., changes of relevant environmental and epigenetic factors).
Implementation of a Pediatric Emergency Telemedicine Program.

OBJECTIVES Our goal was to describe the experiences after the launch of a pediatric emergency telemedicine program at a large, urban, academic medical center. METHODS We launched 3 unique pediatric emergency telemedicine programs at an urban, academic medical center: direct-to-consumer pediatric virtual urgent care, pediatric emergency department (PED) telemedicine follow-up, and telemedicine medical screening examination in the PED. RESULTS We evaluated 84 patients via direct-to-consumer pediatric virtual urgent care with the most common chief complaint related to fever, dermatologic, or respiratory systems; we referred 12% to the PED, and 20% of those required hospital admission. We evaluated 38 patients via PED telemedicine follow-up; we referred 19% back to the PED, and 43% of those required hospital admission. Median duration for a telemedicine encounter was 10 minutes. We screened 3809 patients in the PED using telemedicine medical screening examination. CONCLUSIONS We offer a description of an innovative and comprehensive new pediatric emergency telemedicine program implemented at a large, urban, academic medical center. Our initial findings demonstrate short visit times, antibiotic stewardship, and low rates of PED referral and subsequent admission for patients who use a telemedicine service. We plan to further examine the impact of pediatric emergency telemedicine on the care of children as our program expands.
Exercise Promotes Neurite Extensions from Grafted Dopaminergic Neurons in the Direction of the Dorsolateral Striatum in Parkinson’s Disease Model Rats

Background: Cell transplantation is expected to be a promising treatment for Parkinson’s disease (PD), in which re-innervation of the host striatum by grafted dopamine (DA) neurons is essential. In particular, the dorsolateral part of the striatum is important because it is the target of midbrain A9 DA neurons, which are degenerated in PD pathology. The effect of exercise on the survival and maturation of grafted neurons has been reported in several neurological disease models, but never in PD models. Objective: We investigated how exercise influences cell transplantation for PD, especially from the viewpoint of cell survival and neurite extensions. Methods: Ventral mesencephalic neurons from embryonic (E12.5) rats were transplanted into the striatum of adult 6-OHDA-lesioned rats. The host rats then underwent treadmill training as exercise after the transplantation. Six weeks after the transplantation, they were sacrificed, and the grafts in the striatum were analyzed. Results: The addition of exercise post-transplantation significantly increased the number of surviving DA neurons. Moreover, it promoted neurite extensions from the graft toward the dorsolateral part of the striatum. Conclusions: This study indicates a beneficial effect of exercise after cell transplantation in PD.
Oral health status of children and adolescents with autism spectrum disorder: A systematic review of case-control studies and meta-analysis

Children and adolescents with autism spectrum disorder are thought to be more vulnerable to oral diseases than typically developing individuals due to cariogenic dietary habits, self-injurious behaviors, and increased barriers to dental care services. This review aimed to summarize current evidence comparing the oral health status of people diagnosed with and without autism spectrum disorder. Study selection and screening, data extraction, risk of bias assessment, and quality-of-evidence evaluation was conducted using the Grading of Recommendations Assessment Development and Evaluation approach and performed independently by two reviewers. A total of 16 studies were found eligible for qualitative synthesis and 15 were included in quantitative analysis. When comparing children and adolescents diagnosed with and without autism spectrum disorder, significantly higher prevalence of bruxism was identified. Individuals diagnosed with autism spectrum disorder were also found to have significantly lower salivary pH. However, no statistically significant differences in terms of caries prevalence and severity, oral hygiene and periodontal status, prevalence of malocclusion, dental traumatic injuries, as well as salivary flow rate and buffering capacity were found. The quality of evidence of each outcome was graded as very low mainly due to the overall high risk of bias, considerable heterogeneity, and imprecision. Lay Abstract Children and adolescents diagnosed with Autism Spectrum Disorder (ASD) are thought to be more vulnerable to oral diseases than typically-developing individuals. This is due to their increased barriers to dental care services, self-harm behaviors and dietary habits that may favor tooth decay. In this review, we summarized the current evidence comparing the oral health status of children and adolescents diagnosed with and without ASD. After a systematic search in the literature, we found that the salivary pH of individuals diagnosed with ASD was significantly lower, but the results were not clinically significant that can increase their risks to tooth decay. We also found weak evidence suggesting a higher percentage of children and adolescents diagnosed with ASD having the habit of tooth grinding compared with their neurotypical counterparts. When comparing salivary flow rate, tooth decay, gum diseases, tooth malalignment and tooth trauma; no significant differences were found between the two groups. The findings did not suggest ASD as a predisposing factor to oral diseases: other factors including sugary diet and inadequate oral hygiene may play a more important role. We also call for further research to establish more concrete association between ASD and oral diseases.
VISTA: Coming of age as a multi‐lineage immune checkpoint

The immune response is governed by a highly complex set of interactions among cells and mediators. T cells may be rendered dysfunctional by the presence of high levels of antigen in the absence of co‐stimulation while myeloid cells may be programmed towards an immunosuppressive state that promotes cancer growth and metastasis while deterring tumor immunity. In addition, inhibitory programs driven by immune checkpoint regulators dampen anti‐tumor immunity. The ideal cancer immunotherapy treatment will improve both cross‐priming in the tumor microenvironment and relieve suppression by the inhibitory checkpoints. Recently, blockade of programmed cell death 1 (PD‐1) and cytotoxic T lymphocyte antigen 4 (CTLA‐4) has elicited impressive results, but not in all patients, so additional targets are under investigation. V‐set immunoglobulin domain suppressor of T cell activation (VISTA) is a novel immunoregulatory receptor that is broadly expressed on cells of the myeloid and lymphoid lineages, and is frequently implicated as a poor prognostic indicator in multiple cancers. Importantly, antibody targeting of VISTA uniquely engages both innate and adaptive immunity. This, combined with the expression of VISTA and its non‐redundant activities compared to other immune checkpoint regulators, qualifies VISTA to be a promising target for improving cancer immunotherapy.
Superhydrophobic Surfaces: Insights from Theory and Experiment.

Biomimetic nanocoatings with distinct wettability and versatility have found special enthusiasm in both fundamental research and industrial applications. With the advent of nanotechnology, it is doable to acclimate surface architecture and surface chemistry to attain superhydrophobicity. The uniqueness of superhydrophobic surfaces arises from various phenomenal advances, and its progress is expected to continue for decades in future. In this review, we discuss recent progresses made in defining physical aspects of numerical modeling, experimental practices adopted and applications of superhydrophobic surfaces. First, we revisit various classical models of superhydrophobicity and recent theoretical advances achieved related to the wetting phenomena. Subsequently, we emphasize on various precursors and advance fabrication strategies adopted to fabricate superhydrophobic surfaces. In the following section, we take up various potential applications and appropriate working principles to explain wettability phenomena. Finally, some general conclusions are drawn along with proposed guidelines for designing robust superhydrophobic surfaces.
Broadly Protective Multivalent OspA Vaccine against Lyme Borreliosis, Developed Based on Surface Shaping of the C-Terminal Fragment

The development of vaccines for prevention of diseases caused by pathogenic species can encounter major obstacles if high sequence diversity is observed between individual strains. Therefore, development might be restricted either to conserved antigens, which are often rare, or to multivalent vaccines, which renders the production more costly and cumbersome. In light of this complexity, we applied a structure-based surface shaping approach for the development of a Lyme borreliosis (LB) vaccine suitable for the United States and Europe. ABSTRACT The development of vaccines for prevention of diseases caused by pathogenic species can encounter major obstacles if high sequence diversity is observed between individual strains. Therefore, development might be restricted either to conserved antigens, which are often rare, or to multivalent vaccines, which renders the production more costly and cumbersome. In light of this complexity, we applied a structure-based surface shaping approach for the development of a Lyme borreliosis (LB) vaccine suitable for the United States and Europe. The surface of the C-terminal fragment of outer surface protein A (OspA) was divided into distinct regions, based primarily on binding sites of monoclonal antibodies (MAbs). In order to target the six clinically most relevant OspA serotypes (ST) in a single protein, exposed amino acids of the individual regions were exchanged to corresponding amino acids of a chosen OspA serotype. Six chimeric proteins were constructed, and, based on their immunogenicity, four of these chimeras were tested in mouse challenge models. Significant protection could be demonstrated for all four proteins following challenge with infected ticks (OspA ST1, OspA ST2, and OspA ST4) or with in vitro-grown spirochetes (OspA ST1 and OspA ST5). Two of the chimeric proteins were linked to form a fusion protein, which provided significant protection against in vitro-grown spirochetes (OspA ST1) and infected ticks (OspA ST2). This article presents the proof-of-concept study for a multivalent OspA vaccine targeting a wide range of pathogenic LB Borrelia species with a single recombinant antigen for prevention of Lyme borreliosis.
miR-30a inhibits breast cancer progression through the Wnt/β-catenin pathway.

BACKGROUND miR-30a is a microRNA associated with the progression of malignant tumors such as gastric cancer, colon cancer, prostate cancer, and lung cancer, and can regulate the proliferation and migration of breast cancer (BC) cells in vitro. However, its expression, function, clinical significance and relationship with the Wnt/β-catenin pathway in human BC were still unclear. METHODS Immunohistochemistry, Western blotting and real-time quantitative PCR (RT-qPCR) were used to measure the expressions of miR-30a and β-catenin in 114 pairs of human BC tumor tissues and adjacent normal tissues which were collected from March 2014 to October 2015. The effect of miR-30a on the expression of β-catenin was studied in the MCF-7 cells in vitro. RESULTS The expression levels of miR-30a in human BC tumor tissues were significantly lower than they were in the adjacent normal tissues (P < 0.001), and significantly higher in β-catenin protein (P < 0.001), but there was no significant different in β-catenin mRNA (P = 0.3816). The immunohistochemistry results showed that β-catenin protein was only expressed on the cell membrane in paracancerous normal tissues, but β-catenin protein was expressed on the cell membrane and cytoplasm in BC tumor cells. In addition, there was a significantly negative correlation (r = -0.816, P < 0.001) between the expression miR-30a and β-catenin protein in BC tissues. The age of onset, PR expression, ER expression, and HER-2 expression of the BC patients were not related to miR-30a or β-catenin protein expression (P > 0.05). Tumor diameter, histological grade, lymph node metastasis, TNM stage, and the prognosis of BC patients (P < 0.05) were significantly related to miR-30a or β-catenin protein expression. In MCF-7 cells, miR-30a regulated the accumulation of β-catenin protein by inhibiting the expression of BCL9 in BC cells. CONCLUSION miR-30a was lowly expressed in breast cancer tissues and highly in β-catenin protein, and miR-30a might block the Wnt/β-catenin pathway by inhibiting the accumulation of β-catenin, and then inhibiting breast cancer progression.
Historical Disaster Exposure and Household Preparedness Across the United States

ABSTRACT Objectives: The study determined whether households in disaster-exposed communities were more likely to be prepared. Methods: Three measures of preparedness were created using the 2013 American Housing Survey: cumulative, adequate, and minimal preparedness. Cumulative and adequate preparedness were created based on the existing literature. Minimal preparedness measured whether households had at present food, water, access to a vehicle, and funds with which to evacuate. Disaster exposure was measured using historical FEMA disaster declarations. The various preparedness measures were regressed onto historical disaster exposure, controlling for sociodemographic factors. Results: Across all measures of preparedness, historical disaster exposure was a statistically significant predictor of preparedness. Vulnerable households included those where children or the disabled were present. African-American headed households emerged as vulnerable only when minimal preparedness was assessed. Conclusions: Prior disaster exposure increased household preparedness regardless of how preparedness was defined. However, assessing minimal preparedness may better reflect the changing disaster landscape where more and more households are asked to evacuate or shelter-in-place by policy-makers.
Mitochondrial Ca2+ Uptake Relieves Palmitate-Induced Cytosolic Ca2+ Overload in MIN6 Cells

Saturated fatty acids contribute to β-cell dysfunction in the onset of type 2 diabetes mellitus. Cellular responses to lipotoxicity include oxidative stress, endoplasmic reticulum (ER) stress, and blockage of autophagy. Palmitate induces ER Ca2+ depletion followed by notable store-operated Ca2+ entry. Subsequent elevation of cytosolic Ca2+ can activate undesirable signaling pathways culminating in cell death. Mitochondrial Ca2+ uniporter (MCU) is the major route for Ca2+ uptake into the matrix and couples metabolism with insulin secretion. However, it has been unclear whether mitochondrial Ca2+ uptake plays a protective role or contributes to lipotoxicity. Here, we observed palmitate upregulated MCU protein expression in a mouse clonal β-cell, MIN6, under normal glucose, but not high glucose medium. Palmitate elevated baseline cytosolic Ca2+ concentration ([Ca2+]i) and reduced depolarization-triggered Ca2+ influx likely due to the inactivation of voltage-gated Ca2+ channels (VGCCs). Targeted reduction of MCU expression using RNA interference abolished mitochondrial superoxide production but exacerbated palmitate-induced [Ca2+]i overload. Consequently, MCU knockdown aggravated blockage of autophagic degradation. In contrast, co-treatment with verapamil, a VGCC inhibitor, prevented palmitate-induced basal [Ca2+]i elevation and defective [Ca2+]i transients. Extracellular Ca2+ chelation as well as VGCC inhibitors effectively rescued autophagy defects and cytotoxicity. These observations suggest enhanced mitochondrial Ca2+ uptake via MCU upregulation is a mechanism by which pancreatic β-cells are able to alleviate cytosolic Ca2+ overload and its detrimental consequences.
Assessment of prophylactic antibiotics administration for acute pancreatitis: a meta-analysis of randomized controlled trials

Abstract Background: Recent evidence has shown that prophylactic antibiotic treatment in patients with acute pancreatitis is not associated with a significant decrease in mortality or morbidity. The use and efficacy of prophylactic antibiotic treatment in acute pancreatitis remain controversial. This meta-analysis was conducted to assess whether antibiotic prophylaxis is beneficial in patients with acute pancreatitis. Methods: We searched randomized controlled trials (RCTs) of prophylactic use of antibiotics using Medline (PubMed), Embase, the Cochrane Library, and Web of Science. The data were analyzed using Review Manager 5.3 software. We performed pooled analyses for infected pancreatic necrosis, mortality, surgical intervention, and non-pancreatic infection. Odds ratios (ORs) from each trial were pooled using a random or fixed effects model, depending on the heterogeneity of the included studies. Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity, when necessary. Results: Totally, 11 RCTs involving 747 participants were included, with an intervention group (prophylactic use of antibiotics, n = 376) and control group (n = 371). No significant differences were found regarding antibiotic prophylaxis with respect to incidence of infected pancreatic necrosis (OR, 0.74; 95% confidence interval [CI], 0.50–1.09; P = 0.13), surgical intervention (OR, 0.92; 95% CI, 0.62–1.38; P = 0.70), and morality (OR, 0.71; 95% CI, 0.44–1.15; P = 0.16). However, antibiotic prophylaxis was associated with a statistically significant reduction in the incidence of non-pancreatic infection (OR, 0.59; 95% CI, 0.42–0.84; P = 0.004). Conclusions: Prophylactic antibiotics can reduce the incidence of non-pancreatic infection in patients with AP.