Miracle-dz/UniFAR-FTUs huggingface dataset:
Phylogenetic and Epidemiological Analysis of Measles Viruses in Shenzhen, China from January 2015 to July 2019

Background Measles morbidity and mortality were significantly reduced after the measles vaccine was introduced in China in 1965. However, measles outbreaks easily occur in densely populated areas, especially where there is no universal vaccination. The outbreak that occurred in Shenzhen, the Chinese city with the largest internal immigration, provides a lesson in measles virus mutation and measles prevention. The present study is a phylogenetic analysis of measles viruses and comparison of clinical signs between individuals with and without vaccination. Material/Methods We performed phylogenetic analysis of the nucleoprotein (N) genes of measles virus from 129 measles patients in Shenzhen from January 2015 to July 2019. Phylogenetic trees were constructed using the neighbor-joining method. Results The phylogenetic analysis showed all viruses were classified into genotype H1. In addition, there is often a seasonal measles outbreak in July each year. The clinical data showed that patients who were unvaccinated were more likely to have coughing, chronic bronchitis, conjunctivitis, catarrh, Koplik spots, and diarrhea. Children of migrant workers and those living in mountainous and rural districts accounted for most measles cases. Conclusions Our results showed there was a seasonal measles outbreak in Shenzhen Children’s Hospital. All the measles virus from 129 measles patients were H1 viruses. The clinical signs also showed a difference between unvaccinated and vaccinated patients. Moreover, most of the unvaccinated patients came from migrant worker families. We suggest there is a need for increased health promotion and vaccination programs for migrant workers and people living in remote villages.
Avian Flavivirus Enters BHK-21 Cells by a Low pH-Dependent Endosomal Pathway

Duck Tembusu virus (DTMUV), a pathogenic member of the Flavivirus family, was first discovered in the coastal provinces of South-Eastern China in 2010. Many previous reports have clearly shown that some Flaviviruses utilize several endocytic pathways to enter the host cells, however, the detailed mechanism of DTMUV entry into BHK-21 cells, which is usually employed to produce commercial veterinary vaccines for DTMUV, as well as of other Flaviviruses by serial passages, is still unknown. In this study, DTMUV entry into BHK-21 cells was found to be inhibited by noncytotoxic concentrations of the agents chloroquine, NH4Cl, and Bafilomycin A1, which blocked the acidification of the endosomes. Inactivation of virions by acid pretreatment is a hallmark of viruses that utilize a low-pH-mediated entry pathway. Exposure of DTMUV virions to pH 5.0 in the absence of host cell membranes decreased entry into cells by 65%. Furthermore, DTMUV infection was significantly decreased by chlorpromazine treatment, or by knockdown of the clathrin heavy chain (CHC) through RNA interference, which suggested that DTMUV entry depends on clathrin. Taken together, these findings highlight that a low endosomal pH is an important route of entry for DTMUV.
Secondary hyperparathyroidism: recurrence after total parathyroidectomy with autotransplantation.

BACKGROUND Secondary hyperparathyroidism (sHPTH) is common in patients with end-stage chronic kidney disease. If drug therapy fails, total parathyroidectomy with autotransplantation of parathyroid tissue into the forearm (PTX-AT) is the most widely used procedure. High recurrence rates of sHPTH following PTX-AT are reported in the literature. OBJECTIVE The aim of this study was to evaluate recurrences of sHPTH following PTX-AT in detail in order to develop strategies to prevent recurrences in the future. METHODS This retrospective study analysed a single-centre cohort of 42 patients who underwent PTX-AT for sHPTH at a tertiary centre in Switzerland. Postoperative PTH levels were evaluated to determine the recurrence and persistence rates and the time to recurrence. Furthermore, the peri- and postoperative outcomes were assessed. Patients on dialysis and patients with a functioning kidney transplant suffering tertiary HPTH were analysed separately. RESULTS Intraoperative measurements showed that serum PTH decreased to 6.9% (3.3–15.0%) of the preoperative baseline level. After a median follow-up of 89.5 months (IQR 31.9–152.9), persistence of sHPTH was found in five patients (11.9%) and recurrence in four patients (9.5%), giving a total recurrence rate of 21.4%. CONCLUSION Recurrence of sHPTH after PTX remains a problem, occurring in every fifth patient. In our experience, the introduction of intraoperative PTH measurement has helped to lower the rates of persistence and recurrence. Further reductions in the recurrence rate might be achieved with novel, more accurate pre- and intraoperative imaging techniques.
From eye rolls to punches: experiences of harm from others' drinking among risky-drinking adolescents across Australia.

OBJECTIVES Exploration of experience of harms due to another person's drinking within a demographic particularly vulnerable to these consequences. Importance of study: Largest sampling of young Australian risky drinkers, who are underrepresented in general population surveys. The range of harms due to others' drinking reported here is more comprehensive than documented elsewhere. STUDY TYPE Cross-sectional self-report survey. METHODS Participants were 14-19 years old and screened as being within the riskiest-drinking 25% for their age cohort. The convenience sample of 3465 was recruited primarily by social media advertising. Face-to-face interviews were conducted in all eight Australian capital cities (n = 596), supplemented by online surveys (n = 2869). Past 12-month experience of 13 harms due to others' drinking was assessed by age, gender and perpetrator. RESULTS Females were more likely to experience seven harms, mainly characterised by fear and harassment, including being harassed or bothered at a party or some other private setting (41% vs 34% of males, p < 0.001), being given unwanted sexual attention (71% vs 47%, p < 0.001) and being put in fear (33% vs 20%, p < 0.001). Males were more likely to experience three harms, characterised by aggression: being yelled at, criticised or verbally abused (38% vs 33% of females, p = 0.002), being pushed or shoved (42% vs 28%, p < 0.001) and being physically hurt (17% vs 11%, p < 0.001). Teenagers of a legal alcohol-purchase age were more likely to experience harassment in public settings (49% vs 32-34%, p < 0.001) and unwanted sexual attention (66% vs 51-59%, p < 0.001) compared with younger teenagers. Seven of the harms studied were more likely (p < 0.01) to be perpetrated by people the respondents knew, and five (those associated with fear and aggression) were more likely to be perpetrated by strangers. CONCLUSION Young people who are risky drinkers commonly experience multiple harms from others' drinking. Many of these alcohol harms to others are reported here for the first time, as previous studies of adolescent drinking have focused almost exclusively on the harms young people have experienced from their own drinking. This refocusing on the harms caused by the drinking of others may prompt greater community concern and concomitant calls for better alcohol regulation.
PTPN2 phosphatase deletion in T cells promotes anti‐tumour immunity and CAR T‐cell efficacy in solid tumours

Although adoptive T‐cell therapy has shown remarkable clinical efficacy in haematological malignancies, its success in combating solid tumours has been limited. Here, we report that PTPN2 deletion in T cells enhances cancer immunosurveillance and the efficacy of adoptively transferred tumour‐specific T cells. T‐cell‐specific PTPN2 deficiency prevented tumours forming in aged mice heterozygous for the tumour suppressor p53. Adoptive transfer of PTPN2‐deficient CD8+ T cells markedly repressed tumour formation in mice bearing mammary tumours. Moreover, PTPN2 deletion in T cells expressing a chimeric antigen receptor (CAR) specific for the oncoprotein HER‐2 increased the activation of the Src family kinase LCK and cytokine‐induced STAT‐5 signalling, thereby enhancing both CAR T‐cell activation and homing to CXCL9/10‐expressing tumours to eradicate HER‐2+ mammary tumours in vivo. Our findings define PTPN2 as a target for bolstering T‐cell‐mediated anti‐tumour immunity and CAR T‐cell therapy against solid tumours.
From Local to Global Modeling for Characterizing Calcium Dynamics and Their Effects on Electrical Activity and Exocytosis in Excitable Cells

Electrical activity in neurons and other excitable cells is a result of complex interactions between the system of ion channels, involving both global coupling (e.g., via voltage or bulk cytosolic Ca2+ concentration) of the channels, and local coupling in ion channel complexes (e.g., via local Ca2+ concentration surrounding Ca2+ channels (CaVs), the so-called Ca2+ nanodomains). We recently devised a model of large-conductance BKCa potassium currents, and hence BKCa–CaV complexes controlled locally by CaVs via Ca2+ nanodomains. We showed how different CaV types and BKCa–CaV stoichiometries affect whole-cell electrical behavior. Ca2+ nanodomains are also important for triggering exocytosis of hormone-containing granules, and in this regard, we implemented a strategy to characterize the local interactions between granules and CaVs. In this study, we coupled electrical and exocytosis models respecting the local effects via Ca2+ nanodomains. By simulating scenarios with BKCa–CaV complexes with different stoichiometries in pituitary cells, we achieved two main electrophysiological responses (continuous spiking or bursting) and investigated their effects on the downstream exocytosis process. By varying the number and distance of CaVs coupled with the granules, we found that bursting promotes exocytosis with faster rates than spiking. However, by normalizing to Ca2+ influx, we found that bursting is only slightly more efficient than spiking when CaVs are far away from granules, whereas no difference in efficiency between bursting and spiking is observed with close granule-CaV coupling.
Criteria for tracheostomy decannulation: literature review.

PURPOSE To perform a literature review on the existing international criteria and protocols for tracheostomy decannulation. RESEARCH strategies: Literature review using the PubMed database with the English keywords "Tracheostomy", "Weaning", "Decannulation", "Removal Tube", "Speech, Language and Hearing Sciences", "Intensive Care Units", "Dysphagia", "Swallowing", "Deglutition" and "Deglutition Disorders ". SELECTION CRITERIA Studies published in the last five years (2012 to 2017); studies with human adult population (i.e. ages above 18 years); articles published in English; unrestricted full access articles; and research related to the objectives of the study. DATA ANALYSIS we analyzed sample characterization; professionals involved in the decannulation process; steps of the decannulation process; total time in days of tracheostomy use; total time in days to complete decannulation process; and failure factors to complete the decannulation process. RESULTS Most of the studies investigated tracheostomy decannulation in a sample of males with neurological impairments. The professionals involved in the decannulation process were doctors, speech therapists, physiotherapists and nurses. The most cited decannulation steps were: swallowing assessment; occlusion training; evaluation of air permeability; ability to manipulate secretion and exchange of cannula; cuff deflation and cough training; use of speech valve. CONCLUSION Speech therapists are of great help during the decannulation process, since the assessment of swallowing was one of the decisive steps of the investigated studies. The processes of decannulation includes a multidisciplinary approach and should be performed by the cooperation between physicians, physiotherapists and speech therapists.
Molecular evolution and amino acid characteristics of newly isolated H9N2 avian influenza viruses from Liaoning Province, China

H9N2 is widespread among poultry and humans. Though this subtype is not lethal to either species, it can cause considerable financial losses for farmers and threaten human health. In this study, 10 new H9N2 avian influenza viruses (AIVs) produced by reassortment were isolated from domestic birds in Liaoning Province between March 2012 and October 2014. Nucleotide sequence comparisons indicate that the internal genes of one of these strains are highly similar to those of human H7N9 viruses. Amino acid substitutions and deletions occurred in the HA and NA proteins separately, indicating that all 10 of these isolates may have an enhanced ability to infect mammals. A cross-hemagglutinin inhibition assay conducted with two vaccine strains that are broadly used in China suggests that antisera against vaccine candidates cannot completely inhibit the new isolates. Two of the 10 newly isolated viruses could replicate in respiratory organs of infected BALB/c mice without adaption, suggesting that these isolates can potentially infect mammals. The continued surveillance of poultry is important to provide early warning and control of AIV outbreaks. Our results highlight the high genetic diversity of AIV and the need for more extensive AIV surveillance.
Platelet necrosis mediates ischemic stroke outcome in mice.

Platelets play critical roles in maintaining hemostasis. Dysregulated platelet functions contribute to both the development and progression of ischemic stroke. Utilizing mice with a platelet-specific deletion of cyclophilin D (CypD), a mediator of necrosis, we found that platelet necrosis regulates tissue damage and outcomes during ischemic stroke in vivo. Loss of CypD in platelets significantly enhanced cerebral blood flow, improved neurological and motor functions, and reduced ischemic stroke infarct volume after cerebral ischemia/reperfusion injury in mice. These effects were attributable, at least in part, to platelet-neutrophil interactions. Twenty-four hours after stroke, significantly fewer circulating platelet-neutrophil aggregates were found in CypD-deficient mice. Mice with CypD-deficient platelets also had less neutrophils recruited to their brain relative to wildtype counterparts, and cerebral platelet-neutrophil aggregates were virtually absent in mice with CypD-deficient platelets. Neutrophil depletion in wildtype mice conferred protection from ischemic stroke similarly to mice with CypD-deficient platelets. However, neutrophil depletion in mice with CypD-deficient platelets did not further reduce infarct size. These results suggest necrotic platelets interact with neutrophils to exacerbate brain injury following ischemic stroke. As inhibiting platelet necrosis does not compromise hemostasis, targeting platelet CypD may be a potential therapeutic strategy to limit brain damage following ischemic stroke.
A toolbox of stable integration vectors in the fission yeast Schizosaccharomyces pombe

ABSTRACT Schizosaccharomyces pombe is a widely used model organism to study many aspects of eukaryotic cell physiology. Its popularity as an experimental system partially stems from the ease of genetic manipulations, where the innate homology-targeted repair is exploited to precisely edit the genome. While vectors to incorporate exogenous sequences into the chromosomes are available, most are poorly characterized. Here, we show that commonly used fission yeast vectors, which upon integration produce repetitive genomic regions, give rise to unstable genomic loci. We overcome this problem by designing a new series of stable integration vectors (SIVs) that target four different prototrophy genes. SIVs produce non-repetitive, stable genomic loci and integrate predominantly as single copy. Additionally, we develop a set of complementary auxotrophic alleles that preclude false-positive integration events. We expand the vector series to include antibiotic resistance markers, promoters, fluorescent tags and terminators, and build a highly modular toolbox to introduce heterologous sequences. Finally, as proof of concept, we generate a large set of ready-to-use, fluorescent probes to mark organelles and cellular processes with a wide range of applications in fission yeast research. This article has an associated First Person interview with the first author of the paper. Summary: We establish a new vector series to efficiently and stably introduce DNA sequences into the fission yeast genome, and use it to generate a set of fluorescent cell biology probes.
Total sleep deprivation increases pain sensitivity, impairs conditioned pain modulation and facilitates temporal summation of pain in healthy participants

Chronic pain patients often suffer from insomnia or impaired sleep which has been associated with increased pain sensitivity, but a limited amount of studies have investigated the effects of total sleep deprivation on central pain mechanisms. Therefore, the aim of this study was to determine the effects of total sleep deprivation on temporal summation, conditioned pain modulation, thermal and pressure pain sensitivity in healthy participants. Twenty-four healthy participants took part in this two-session trial. The measurements were conducted after a night of habitual sleep (baseline) and following 24 hours of total sleep deprivation. Detection thresholds for cold and warmth and pain thresholds for cold and heat were assessed. Cuff induced pressure pain detection and tolerance thresholds, temporal summation and conditioned pain modulation were assessed with user-independent, computer-controlled cuff algometry. Conditioned pain modulation was significantly impaired, temporal summation was significantly facilitated and pain sensitivity to pressure and cold pain were significantly increased at follow-up compared with baseline. In conclusion, this study found that one night of total sleep deprivation impaired descending pain pathways, facilitated spinal excitability and sensitized peripheral pathways to cold and pressure pain. Future studies are encouraged to investigate if sleep therapy might normalize pain sensitivity in sleep-deprived chronic pain patients.
Prevalence of hypothermia in the first hour of life of premature infants weighing ≤ 1500g.

OBJECTIVE To analyze the prevalence of hypothermia in the first hour of life of preterm infants with birth weight 1,500 g or less. METHOD A cross-sectional study performed in a Neonatal Intensive Care Unit. Data obtained from 359 computerized records of premature infants admitted between 2012 and 2016. Descriptive Statistics and Poisson Regression were used. RESULTS Premature infants (66.9%) presented hypothermia in the first hour of life, with axillary temperature of 36. 2ºC (35.7-36.6), associated with: diagnosis of preeclampsia (p = 0.001), small for gestational age (p = 0.029), and the need for chest compression in the delivery room (p = 0.001). In cases of peri-intraventricular hemorrhage grade III (75%) and death (78.9%), there was a prevalence of premature infants with hypothermia in the first hour of life. CONCLUSION Hypothermia in the first hour of life was prevalent in preter m infants, being associated with clinical complications. The prevention of hypothermia in the first hour of life is fundamental in the reduction of diseases related to prematurity.
Measuring Diet Intake and Gastrointestinal Symptoms in Irritable Bowel Syndrome: Validation of the Food and Symptom Times Diary

INTRODUCTION: Patients with irritable bowel syndrome (IBS) identify food as a trigger for the onset or worsening of gastrointestinal symptoms. Despite this, there is no published validated contemporaneous food and symptom diary to investigate the association between diet and IBS symptoms. The objective of this prospective observational study was to assess the construct validity of a novel food diary and symptom questionnaire, the Food and Symptom Times (FAST) diary, and the predictive validity of the food diary component with relation to fiber and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols consumption and subsequent gastrointestinal symptoms. METHODS: Fifty-one participants with IBS completed the FAST diary and several legacy instruments. The relationship between the FAST gastroenterological symptoms and legacy instruments was examined using Spearman correlation coefficients. Further statistical analysis investigated the relationship between diet and postprandial gastrointestinal symptoms. RESULTS: Consistent with a priori predictions, the FAST symptoms showed moderate correlations with the most similar Patient-Reported Outcome Measurement Information System gastrointestinal scales (0.328–0.483, P < 0.05) and the most similar Gastrointestinal Symptom Rating Scale questions (0.303–0.453, P < 0.05), with the exception of the weakly correlated subscale constipation for both instruments (−0.050 to −0.119, P > 0.05). The IBS-Quality of Life instrument showed moderate correlations with the FAST symptom abdominal swelling/distension (0.313–0.416, P < 0.05). The consumption of a high fermentable oligosaccharides, disaccharides, monosaccharides, and polyols meal was associated with participants with IBS-D experiencing abdominal bloating and participants with IBS-C not experiencing abdominal swelling (P < 0.05). The consumption of fiber was correlated with abdominal fullness and bloating in participants with IBS-C (P < 0.05). DISCUSSION: The FAST diary validly measures gastrointestinal symptoms as they occur in people with IBS and correlates these symptoms with specific aspects of diet.
Influenza B viral load analysis in patients with acute respiratory infection from a tertiary hospital in Brazil

Currently, 2 genotypes of Influenza B viruses (IFB) are cocirculating in humans: Victoria (VIC) and Yamagata (YAM). Infection and viral load (VL) were analyzed in 105 genotyped IFB (59 VIC and 46 YAM) out of 3452 respiratory samples from immunodepressed (ID), immunocompetent (IC) including outpatients (OP) and hospitalized patients (HP) attended during 2001‐2013 at São Paulo Hospital. VL (Log10 RNA copies/mL) calculation was possible in 78 samples (47 VIC, 31 YAM). The age group of 12 to 18 years presented the highest detection (14.13%). Rates of infection among groups were of 3.67% (IC), 1.68% (ID), 3.50% (OP), 0.6% (HP), and VLs varied from 2.8 to 10.13 with no difference regarding age, immune status, and disease severity. From 10 OP vaccinated against influenza, 8 (7 children, 1 ID) received a matching strain shot (VIC), and 2 a monovalent influenza A H1N1pdm09. Those patients presented a VL of 6.31 ± 1.62 (mean ± SD). IFB infection rates follow an age pattern, but VL seems not to be related to frequency or clinical outcome. IFB patients with previous immunization could point to some protection for VIC infections since there was no HP. Other immunological aspects, such as lineage infection immune priming, previous infections, and vaccinations, should be further investigated.