Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidemiology and Mortality-Associated Factors of Invasive Fungal Disease in Elderly Patients: A 20-Year Retrospective Study from Southern China

Introduction Invasive fungal disease (IFD) is a life-threatening infection. The epidemiology and clinical features of IFD in the elderly population are less discussed. The aim of this study was to explore the epidemiology and mortality-associated factors for IFD in the elderly inpatients. Methods A retrospective study enrolling 512 elderly inpatients from The First Affiliated Hospital of Sun Yat-sen University during the last two decades was performed. Results The annual prevalence of IFD was 0.1–0.5%. Candidiasis was the most common (236/521, 45.3%). An increasing trend was observed in aspergillosis from 11.1% in year 1998 to 28.8% in year 2018. The common infective sites of candidiasis were abdominal cavity (83/236, 35.2%) and bloodstream (55/236, 23.3%). Invasive aspergillosis mainly developed in the sinus (74/149, 49.7%) and lung (65/149, 43.6%). Patients with diabetes mellitus (DM) (59/126, 46.8%), solid organ malignancy (84/114, 73.7%), chronic kidney disease (CKD) (40/62, 64.5%) or receiving operation (109/147, 74.1%) were prone to develop candidiasis, while aspergillosis was usually complicated in patients with chronic obstructive pulmonary disease (COPD) (25/51, 49.0%). The all-cause mortality rate was 25.9% (135/521), and patients aged ≥80 years were the riskiest (20/51, 39.2%). Lymphopenia (59.5% vs 17.3%, P<0.001) was significant in deceased patients with mold infection. Higher proportion of non-survivors with invasive candidiasis received central venous catheterization (CVC) (68.4% vs 40.6%, P<0.001) or indwelling urinary catheter (68.4% vs 46.3%, P=0.001). Conclusion IFD is a life-threatening complication especially in the oldest-old. Surveillance on lymphopenia, prompt treatment and reduce invasive procedures could benefit the prognosis.
Effects of human recombinant granulocyte-colony stimulating factor treatment during in vitro culture on porcine pre-implantation embryos

Granulocyte-colony stimulating factor (G-CSF), a pleiotropic cytokine, belongs to the hematopoietic growth factor family. Recent studies have reported that G-CSF is a predictive biomarker of oocyte and embryo developmental competence in humans. The aim of our study was to determine whether CSF3 and its receptor (CSF3R) were expressed in porcine maternal reproductive tissues (oviduct and uterus), cumulus cells, and embryos and to investigate the effects of human recombinant G-CSF (hrG-CSF) supplementation during in vitro culture (IVC) on the developmental competence of pre-implantation embryos. To do this, we first performed reverse-transcription polymerase chain reaction (RT-PCR). Second, we performed parthenogenetic activation (PA), in vitro fertilization (IVF), and somatic cell nuclear transfer (SCNT) to evaluate the embryonic developmental potential after hrG-CSF supplementation based on various concentrations (0 ng/mL, 10 ng/mL, 50 ng/mL, and 100 ng/mL) and durations (Un-treated, Days 0–3, Days 4–7, and Days 0–7) of IVC. Finally, we examined transcriptional levels of several marker genes in blastocysts. The results of our study showed that CSF3 transcript was present in all samples we assessed. CSF3-R was also detected, except in cumulus cells and blastocysts from PA. Furthermore, 10 ng/mL and Days 0–7 were the optimal concentration and duration for the viability of in vitro embryonic development, especially for SCNT-derived embryos. The rate of blastocyst formation and the total cell number of blastocysts were significantly enhanced, while the number and index of apoptotic nuclei were significantly decreased in optimal condition groups compared to others. Moreover, the transcriptional levels of anti-apoptotis- (BCL2), proliferation- (PCNA), and pluripotency- (POU5F1) related genes were dramatically upregulated. In conclusion, for the first time, we demonstrated that CSF3 and CSF3R were expressed in porcine reproductive organs, cells, and embryos. Additionally, we determined that hrG-CSF treatment improved porcine embryonic development capacity in vitro.
Helicobacter pylori Gastritis in Children—The Link between Endoscopy and Histology

Background: The management of Helicobacter pylori (H. pylori) infection raises important challenges, still being the most common chronic infection worldwide in all age groups. In high-prevalence regions, paediatric patients need a specific focus, as the acquisition of the infection takes place in childhood. The objective of this study was to analyze the endoscopic and histopathologic changes of the gastric mucosa in H. pylori infected children. Material and Methods: A retrospective study was performed on consecutive paediatric patients, ranging from 0 to 18 years of age, who underwent an upper gastrointestinal endoscopy (UGE) for a period of 5 years, regardless of their symptomatology. Endoscopy reports and histological slides were reviewed and clinical, endoscopic, and histologic data were recorded. Results: A total of 248 patients were included in the study, 82 (33.06%) of them being H. pylori infected. There was no difference in age and symptoms between the infected and noninfected group. A significant association was found between the H. pylori infection and histopathological parameters such as acute and chronic inflammatory infiltrate. The bacterial load influences the intensity of inflammation (p < 0.001). The chronic inflammation was predominant, only 23.2% of the patients displayed acute inflammation (p < 0.0001). The topographic distribution of inflammation was dominated by pangastritis (p = 0.04) with 58.6% of the patients presenting similar degrees of inflammation both in the antrum and corpus. Conclusion: Endoscopic features such as nodularity of the antral mucosa (p < 0.05) along with histological findings as lymphoid follicles (p < 0.05) are suggestive of H. pylori infection. However, the concordance between the endoscopic and histological diagnosis is still far from perfect (Cohen’s k coefficient = 0.42), maintaining the need for an invasive approach in children.
Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes: Evaluation of Hepatic Fibrosis and Steatosis Using Fibroscan

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of non-alcoholic fatty liver disease (NAFLD) and might eventually progress to advanced fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Recommendations on whether to screen for NAFLD in diabetic patients remains conflicted between major guidelines. Transient elastography using FibroScan with CAP (controlled attenuation parameter) can assess both liver steatosis and fibrosis simultaneously. This paper took a new look at the prevalence of NAFLD and the severity of fibrosis among T2DM patients in Vietnam. The study was conducted using a cross-sectional design in T2DM adults who attended Dai Phuoc Ho Chi Minh Polyclinic and Polyclinic of Pham Ngoc Thach University of Medicine. Liver steatosis and fibrosis was assessed by FibroScan. NAFLD was diagnosed if CAP > 233 dB/m (steatosis > 5%). Data were analyzed using STATA 12 software program. We found that a total of 307 type 2 diabetic patients qualified for the study’s criteria. The prevalence of NAFLD in T2DM patients based on FibroScan was 73.3%. Rates of mild, moderate and severe steatosis were 20.5%, 21.8% and 30.9%, respectively. The prevalence of significant fibrosis (≥ F2), advanced fibrosis (≥ F3) and cirrhosis (F4) was 13.0%, 5.9% and 3.6%, respectively. On multivariate analysis, aspartate aminotransferase (AST) (OR: 1.067; 95% CI: 1.017–1.119; p = 0.008) and platelet levels (OR: 0.985; 95% CI: 0.972–0.999; p = 0.034) were independent of risk factors of advanced fibrosis. Thus, our study supports screening for NAFLD and for evaluating the severity of liver fibrosis in T2DM patients.
Novel instrumental markers of proximal scleroderma provided by imaging photoplethysmography

Objective: Instrumental identification of proximal scleroderma, which is necessary for the early diagnosis of systemic sclerosis (SSD), has not yet been developed. The aim of this study was to assess the potential diagnostic value of the imaging photoplethysmography (IPPG) method in patients with SSD. Approach: The study enrolled 19 patients with SSD and 21 healthy subjects matched by age and sex with the patients. Spatial distribution of capillary-blood-flow parameters and their dynamics was estimated in the facial area of patients and subjects. In the IPPG system, a 40 s video of the subject’s face illuminated by green polarized light was recorded with a monochrome digital camera in synchronization with the electrocardiogram. Experimental data were processed using custom software allowing assessment of an arrival time of the blood pressure wave (PAT), an amplitude of pulsatile component (APC) of the photoplethysmographic (PPG) waveform, and their variability. Main results: Our study has revealed a significant increase in PAT variability in patients with SSD compared to the control group: 52 ± 47 ms vs 24 ± 13 ms (P =0.01). Similarly, the variability of the PPG-pulse shape was larger in patients with SSD: 0.13 ± 0.07% vs 0.09 ± 0.02% (P < 0.001). In addition, patients with scleroderma showed a significantly greater degree of asymmetry of the APC parameter than the control group: 17.7 ± 9.7 vs 7.9 ± 5.0 (P < 0.001). At the same time, no correlation was found between the PPG waveform parameters and either the form or duration of the disease. Also, no relationship between the characteristics of the PPG waveform and the modified Rodnan skin score was found. Significance: Novel instrumental markers found in our pilot study showed that the IPPG method can be used for diagnosing SSD in the early stages of the disease.
Tauopathy Analysis in P301S Mouse Model of Alzheimer Disease Immunized with DNA and MVA Poxvirus-Based Vaccines Expressing Human Full-Length 4R2N or 3RC Tau Proteins

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive memory loss and cognitive decline that has been associated with an accumulation in the brain of intracellular neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein, and extracellular senile plaques formed by β-amyloid peptides. Currently, there is no cure for AD and after the failure of anti β-amyloid therapies, active and passive tau immunotherapeutic approaches have been developed in order to prevent, reduce or ideally reverse the disease. Vaccination is one of the most effective approaches to prevent diseases and poxviruses, particularly modified vaccinia virus Ankara (MVA), are one of the most promising viral vectors used as vaccines against several human diseases. Thus, we present here the generation and characterization of the first MVA vectors expressing human tau genes; the full-length 4R2N tau protein or a 3RC tau fragment containing 3 tubulin-binding motifs and the C-terminal region (termed MVA-Tau4R2N and MVA-Tau3RC, respectively). Both MVA-Tau recombinant viruses efficiently expressed the human tau 4R2N or 3RC proteins in cultured cells, being detected in the cytoplasm of infected cells and co-localized with tubulin. These MVA-Tau vaccines impacted the innate immune responses with a differential recruitment of innate immune cells to the peritoneal cavity of infected mice. However, no tau-specific T cell or humoral immune responses were detected in vaccinated mice. Immunization of transgenic P301S mice, a mouse model for tauopathies, with a DNA-Tau prime/MVA-Tau boost approach showed no significant differences in the hyperphosphorylation of tau, motor capacity and survival rate, when compared to non-vaccinated mice. These findings showed that a well-established and potent protocol of T and B cell activation based on DNA/MVA prime/boost regimens using DNA and MVA vectors expressing tau full-length 4R2N or 3RC proteins is not sufficient to trigger tau-specific T and B cell immune responses and to induce a protective effect against tauopathy in this P301S murine model. In the pursuit of AD vaccines, our results highlight the need for novel optimized tau immunogens and additional modes of presentation of tau protein to the immune system.
Aberrant Expression and Subcellular Localization of PER2 Promote the Progression of Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma, one of the most prevalent cancer types in the world, has been confirmed under the influence of a key circadian gene, PER2, whose role has been identified in the development of some other types of cancers. However, the mechanism through which PER2 regulates the progress of OSCC remains largely unknown. In this study, we showed that besides the abnormal expression and subcellular localization of PER2 observed in OSCC tissues and cells as expected, these anomalous changes also existed in the adjacent noncancerous tissues, which was a novel finding in our research. The phase of PER2 rhythmic expression pattern in OSCC cells was later than that in oral keratinocytes in the protein level. In addition, we demonstrated that PER2 played as a resistant factor in the development of OSCC by upregulating TP53 and inhibiting epithelial-mesenchymal transition in vitro and in vivo. Taken together, our results identified that the development of OSCC is closely associated with PER2, the aberrant expression and subcellular localization of which facilitates the malignant progress.
Serum Platelet-Derived Growth Factor Is Significantly Lower in Patients with Lung Cancer and Continued to Decrease After Platinum-Based Chemotherapy

Objective This study aimed to investigate the diagnosis and prediction of serum platelet-derived growth factor (PDGF) level in patients with lung cancer (LC). Methods Serum concentrations of PDGF-AA and PDGF-AB/BB were determined via Luminex assay in 210 patients with non-small cell lung cancer (NSCLC), 33 patients with small cell lung cancer (SCLC), and 168 healthy controls. Results The serum levels of PDGF-AA and PDGF-AB/BB were lower in patients with NSCLC (P < 0.05) and SCLC (P < 0.05), compared to healthy controls. The concentration of PDGF-AA or PDGF-AB/BB continued to markedly decrease in NSCLC after therapy with platinum-based chemotherapy (P < 0.05). The median survival times were 29 and 38 months in patients with NSCLC who received PDGF-AA < 30 ng/mL and PDGF-AA ≥ 30 ng/mL (P = 0.0078), and 26 and 38 months in patients with NSCLC who received PDGF-AB/BB < 42 ng/mL and PDGF-AB/BB ≥ 42 ng/mL (P = 0.0001), respectively. At the individual protein level, PDGF-AA and PDGF-AB/BB had better diagnostic values for NSCLC (AUC = 0.905, AUC = 0.922, respectively). Conclusion Serum PDGF may be a potential biomarker for diagnosis of patients with NSCLC and SCLC. However, the prognostic value of serum PDGF in patients with NSCLC harboring mutations and different therapies requires additional investigation.
High Levels of Kinesiophobia at Discharge from the Hospital May Negatively Affect the Short-Term Functional Outcome of Patients Who Have Undergone Knee Replacement Surgery

Background: Kinesiophobia is a psycho-cognitive factor that hampers recovery after orthopedic surgery. No evidence exists on the influence of kinesiophobia on the short-term recovery of function in patients with knee replacement (KR). Therefore, the aim of the present study is to investigate the impact of kinesiophobia on short-term patient-reported outcomes (PROMs) and performance-based measures (PBMs). Methods: Forty-three KR patients filled in the Tampa scale for kinesiophobia (TSK) at time of discharge. Patients with TSK ≥ 37 were allocated to the kinesiophobia group (n = 24), others to the no-kinesiophobia group (n = 19). Patients were asked to complete PROMs and to execute PBMs at discharge and at 6-weeks follow-up. An independent samples t-test was used to compare group differences for PROMs and PBMs at both measurement sessions. Multiple linear regression analysis models were used to model PBM outcomes from age, pain and TSK scores. Results: Significant differences were observed between groups for PROMs and PBMs. Kinesiophobia significantly contributed to the reduced functional outcomes. Conclusion: At discharge from the hospital, 55.8% of KR patients demonstrated high levels of kinesiophobia (TSK ≥ 37). This may negatively influence short-term recovery of these patients, by putting them at higher risk for falling and reduced functionality.
Emergence of an NDM-5-Producing Escherichia coli Sequence Type 410 Clone in Infants in a Children’s Hospital in China

Purpose Outbreaks of infection due to carbapenem-resistant Enterobacterales (CRE), including New Delhi metallo-β-lactamase (NDM)-producing Escherichia coli, have been increasingly reported worldwide, primarily in adults and rarely in children. The goal of this study was to characterize an outbreak of infection caused by NDM-5-producing E. coli in a children’s hospital in China. Methods A total of 86 CRE isolates were collected from 85 hospitalized children between June 2017 and May 2018. These isolates were subjected to multiple phenotypic and molecular tests, including in vitro antimicrobial susceptibility testing, PCR, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and whole-genome sequencing (WGS). Results Among the 86 CRE isolates, we identified 9 NDM-5-producing E. coli isolates, with 5 of them sharing the same PFGE pattern, same MLST type (ST410), same plasmid replicon type (IncFII), and nearly the same set of additional resistance genes. All 9 isolates were resistant to most antimicrobial agents, including carbapenems, cephalosporins, and levofloxacin, while being sensitive to trimethoprim/sulfamethoxazole, amikacin, tigecycline, and colistin. According to the clinical background, all 9 isolates were collected in a period of < 3 months from infants among whom there was overlap in the time of hospitalization. None of them had a travel history. Conclusion Our analysis suggests an outbreak of clonal dissemination, presumably due to nosocomial transmission. This study represents the first documented outbreak of NDM-5-producing E. coli mediated by IncFII in infants. Close monitoring is urgently needed to prevent and control the spread of this difficult-to-treat superbug.
“A Blessing and a Curse:” Opioid Users' Perspectives on Naloxone and the Epidemic of Opioid Overdose

Abstract Background: To address the alarming rise in opioid overdose deaths, states have increased public access to the overdose reversal medication, naloxone. While some studies suggest that increased naloxone accessibility reduces opioid overdose deaths, others raise concerns about unintended consequences, such as increases in risky drug use and opioid re-use post-overdose to counter naloxone-induced withdrawal symptoms. Few studies have examined the impact of expanded naloxone access on the attitudes and behaviors of opioid users. Methods: In this qualitative study, we conducted in-depth, semi-structured interviews with 36 English-speaking opioid users 18+ years of age. Informants were recruited from an urban methadone clinic, a needle exchange program and a residential treatment program. The approximately hour-long interviews focused on users’ attitudes and behaviors surrounding naloxone, opioid use and overdose. Transcribed audio-recordings of interviews were analyzed using NVivo. Results: Informants were ambivalent about naloxone, widely acknowledging its life-saving benefits while reporting such negative effects as severe withdrawal symptoms and the promotion of riskier drug use. Naloxone-induced withdrawal, coupled with misperceptions about naloxone’s pharmacological effects, prompted overdose survivors to rapidly re-use opioids and refuse hospitalization following an overdose reversal. About half the sample believed naloxone led to greater risk-taking by others, such as fentanyl use or use in higher quantities, but did not endorse riskier drug use themselves. Conclusions: The results suggest the need for targeted education about the pharmacological effects of naloxone and better strategies for managing naloxone-induced withdrawal. Future research should focus on the extent to which naloxone is associated with greater opioid risk-taking.
Built environment correlates of physical activity in low- and middle-income countries: A systematic review

Insufficient physical activity (PA) is the fourth major risk factor for many non-communicable diseases and premature mortality worldwide. Features of the built environment (BE) play a considerable role in determining population PA behaviors. The majority of evidence for PA-BE relationships comes from high-income countries and may not be generalizable to low- and middle-income countries (LMICs). We aim to systematically review the literature and assess the associations between perceived and/or objective BE characteristics and PA domains in LMICs. This review adopted a systematic search strategy for English language articles published between January 2000 and June 2019 from four electronic databases—Medline, Embase, Web of Science and PubMed—adhering to the PRISMA guidelines. Studies addressing the associations between self-reported and/or objective BE and PA were only included if they were conducted in LMICs, according to the World Bank classification list. Articles investigating PA-BE relationships across any age groups were included, and all study designs were eligible, except for qualitative studies and reviews. Thirty-three studies were included for evidence synthesis. Cross-sectional studies were the most prevailing study design (97%), revealing a notable gap in longitudinal PA-BE research in LMICs. A majority of the BE factors were not associated with different PA domains while others (e.g., density, proximity to services, aesthetics) exhibited an inconsistent association. Land-use mix diversity was positively associated with transport PA and the presence of recreation facilities resulted in an increase in PA during leisure-time. Increased safety from crime at night consistently increased total PA and walking levels. Research exploring the associations between BE attributes and PA behaviors in LMICs appears to be limited and is primarily cross-sectional. Longitudinal research studies with objective measures are needed for inferring well-grounded PA-BE causal relationships and informing the design of evidence-based environmental interventions for increasing PA levels in LMICs.
Aryl Hydrocarbon Receptor in Post-Mortem Hippocampus and in Serum from Young, Elder, and Alzheimer’s Patients

One of the characteristics of the cerebral aging process is the presence of chronic inflammation through glial cells, which is particularly significant in neurodegeneration. On the other hand, it has been demonstrated that the aryl hydrocarbon receptor (AHR) participates in the inflammatory response. Currently, evidence in animal models shows that the hallmarks of aging are associated with changes in the AHR levels. However, there is no information concerning the behavior and participation of AHR in the human aging brain or in Alzheimer’s disease (AD). We evaluated the expression of AHR in human hippocampal post-mortem tissue and its association with reactive astrocytes by immunohistochemistry. Besides this, we analyzed through ELISA the AHR levels in blood serum from young and elder participants, and from AD patients. The levels of AHR and glial fibrillar acid protein were higher in elder than in young post-mortem brain samples. AHR was localized mainly in the cytosol of astrocytes and displayed a pattern that resembles extracellular vesicles; this latter feature was more conspicuous in AD subjects. We found higher serum levels of AHR in AD patients than in the other participants. These results suggest that AHR participates in the aging process, and probably in the development of neurodegenerative diseases like AD.