Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of Giant Kelp, Macrocystis pyrifera, Driven by Marine Heatwaves and Exacerbated by Poor Water Clarity in New Zealand

Marine heatwaves (MHW) are becoming stronger and more frequent across the globe. MHWs affect the thermal physiology of all biological organisms, but wider ecosystem effects are particularly impactful when large habitat-forming foundation species such as kelps are affected. Many studies on impacts from MHWs on kelps have focused on temperature effects in isolation, except for a few studies that have integrated co-occurring stress from grazers, wave exposure and nutrient limitation. It is likely that many stressors act in concert with MHWs and exacerbate their effects. Here we analyzed satellite images over 60 months to assess temporal changes in abundance of surface canopies of the giant kelp Macrocystis pyrifera in the New Zealand coastal zone. The analysis encompassed the most extreme MHW on record (2017/18), across a 6° latitudinal gradient of four regions southward from the northern distributional limit of Macrocystis along mainland New Zealand. We tested the association of surface canopy cover of Macrocystis with sea surface temperature, temperature anomalies, chlorophyll-a (a proxy for nutrient availability) and water clarity (diffuse attenuation coefficient). We found a reduced cover of Macrocystis across all regions during and after the 2017/18 MHW, with least impact at the most southern region where the maximum temperatures did not exceed 18°C. There was also an important and significant interaction between temperature and water clarity, showing that temperature-induced kelp loss was greater when water clarity was poor. These results show that notable negative effects occurred across the coastal range of this foundation species and highlight the importance of studying MHW effects across latitudinal gradients and in concert with other co-occurring stressors.
Novel Role of Gestational Hydralazine in Limiting Maternal and Dietary Obesity-Related Chronic Kidney Disease

Background Maternal obesity is a risk factor for chronic kidney disease (CKD) in offspring, underpinning the theory of the developmental origins of health and disease. DNA methylation has been implicated in the programming of adult chronic disease by maternal obesity, therefore, DNA demethylating agents may mitigate offspring risk of disease. In rodent models, low-dose hydralazine has previously been shown to reduce renal fibrosis via DNA demethylation. We used mouse models of maternal obesity and offspring obesity to determine whether administration of low-dose hydralazine during gestation can prevent fetal programming of CKD in offspring. Methods Female C57BL/6 mice received high fat diet (HFD) or chow prior to mating, during gestation and lactation. During gestation, dams received subcutaneous hydralazine (5 mg/kg) or saline thrice-weekly. Male offspring weaned to HFD or chow, which continued until endpoint at 32 weeks. Biometric and metabolic parameters, renal global DNA methylation, renal functional and structural changes, and renal markers of fibrosis, inflammation and oxidative stress were assessed at endpoint. Results Offspring exposed to maternal obesity or diet-induced obesity had significantly increased renal global DNA methylation, together with other adverse renal effects including albuminuria, glomerulosclerosis, renal fibrosis, and oxidative stress. Offspring exposed to gestational hydralazine had significantly reduced renal global DNA methylation. In obese offspring of obese mothers, gestational hydralazine significantly decreased albuminuria, glomerulosclerosis, and serum creatinine. Obese offspring of hydralazine-treated lean mothers displayed reduced markers of renal fibrosis and oxidative stress. Conclusion Gestational hydralazine decreased renal global DNA methylation and exerted renoprotective effects in offspring. This supports a potential therapeutic effect of hydralazine in preventing maternal obesity or dietary obesity-related CKD, through an epigenetic mechanism.
PD-1 and TIGIT Are Highly Co-Expressed on CD8+ T Cells in AML Patient Bone Marrow

Despite the great success of immune-checkpoint inhibitor (ICI) treatment for multiple cancers, evidence for the clinical use of ICIs in acute myeloid leukemia (AML) remains inadequate. Further exploration of the causes of immune evasion in the bone marrow (BM) environment, the primary leukemia site, and peripheral blood (PB) and understanding how T cells are affected by AML induction chemotherapy or the influence of age may help to select patients who may benefit from ICI treatment. In this study, we comprehensively compared the distribution of PD-1 and TIGIT, two of the most well-studied IC proteins, in PB and BM T cells from AML patients at the stages of initial diagnosis, complete remission (CR), and relapse-refractory (R/R) disease after chemotherapy. Our results show that PD-1 was generally expressed higher in PB and BM T cells from de novo (DN) and R/R patients, while it was partially recovered in CR patients. The expression of TIGIT was increased in the BM of CD8+ T cells from DN and R/R patients, but it did not recover with CR. In addition, according to age correlation analysis, we found that elderly AML patients possess an even higher percentage of PD-1 and TIGIT single-positive CD8+ T cells in PB and BM, which indicate greater impairment of T cell function in elderly patients. In addition, we found that both DN and R/R patients accumulate a higher frequency of PD-1+ and TIGIT+ CD8+ T cells in BM than in corresponding PB, indicating that a more immunosuppressive microenvironment in leukemia BM may promote disease progression. Collectively, our study may help guide the combined use of anti-PD-1 and anti-TIGIT antibodies for treating elderly AML patients and pave the way for the exploration of strategies for reviving the immunosuppressive BM microenvironment to improve the survival of AML patients.
Feasibility and Safety of Permanent Left Bundle Branch Pacing in Patients With Conduction Disorders Following Prosthetic Cardiac Valves

Background: The feasibility and safety of left bundle branch pacing (LBBP) in patients with conduction diseases following prosthetic valves (PVs) have not been well described. Methods: Permanent LBBP was attempted in patients with PVs. Procedural success and intracardiac electrical measurements were recorded at implant. Pacing threshold, complications, and echocardiographic data were assessed at implant and follow-up visit. Results: Twenty-two consecutive patients with atrioventricular (AV) conduction disturbances (10 with AV nodal block and 12 with infranodal block) underwent LBBP. The PVs included aortic valve replacement (AVR) in six patients, mitral valve repair or replacement (MVR) with tricuspid valve ring (TVR) in four patients, AVR with TVR in one patient, AVR with MVR plus TVR in three patients, transcatheter aortic valve replacement (TAVR) in five patients, and MVR alone in three patients. LBBP succeeded in 20 of 22 (90.9%) patients. LBB potential was observed in 15 of 22 (68.2%) patients, including 10 of 15 (66.7%) patients with AVR/TAVR and five of seven (71.4%) patients without AVR/TAVR. AVR and TVR served as good anatomic landmarks for facilitating the LBBP. The final sites of LBBP were 17.9 ± 1.4 mm inferior to the AVR and 23.0 ± 3.2 mm distal and septal to the TVR. The paced QRS duration was 124.5 ± 13.8 ms, while the baseline QRS duration was 120.0 ± 32.5 ms (P = 0.346). Pacing threshold and R-wave amplitude at implant were 0.60 ± 0.16 V at 0.5 ms and 11.9 ± 5.5 mV and remained stable at the mean follow-up of 16.1 ± 10.8 months. No significant exacerbation of tricuspid valve regurgitation was observed compared to baseline. Conclusion: Permanent LBBP could be feasibly and safely obtained in the majority of patients with PVs. The location of the PV might serve as a landmark for guiding the final site of the LBBP. Stable pacing parameters were observed during the follow-up.
A 4-Gene Signature Associated With Recurrence in Low- and Intermediate-Risk Endometrial Cancer

Background The molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer. Methods A case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the nCounter® PanCancer Pathways Panel, which contains 770 genes. Results The expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: FN1, DUSP4, LEF1, and SMAD9. The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%. Conclusion We identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer.
Inhalation Exposure to Atmospheric Nanoparticles and Its Associated Impacts on Human Health: A Review

Nanoparticles (NPs) are receiving an increasing attention from many scientific communities due to their strong influence on human health. NPs are an important marker of air pollution caused by a variety of natural and anthropogenic sources. Due to their ultrafine size, they can be suspended in the atmosphere for a long time and can thus travel larger distances and cause several health issues after exposure. A variety of NPs that are found in indoor and outdoor settings cause respiratory and cardiovascular diseases. Exposure to NPs through active and passive smoking and household and occupational subjection is reported with thick septum, shortness of breath, and a high level of interleukin protein and tumour necrosis factor (TNF-α) that cause tumour generation in the exposed population. This comprehensive review summarises NPs' source, exposure, and impact on different organ systems. Respiratory models (experimental and computational) used to determine the particle's deposition, airflow transport, and health impact are also discussed. Further, muco-ciliary escalation and macrophage activity, the body's clearance mechanisms after exposure to NPs, have been mentioned. An in-depth analysis of exposure to NPs through inhalation and their health impact has been provided with detailed insights about oxidative stress, inflammation, genotoxicity, and tumourigenicity. Overall, this review offers scientific evidence and background for researchers working in the field of epidemiology, biochemistry, and toxicological studies with reference to atmospheric nanoparticles.
Upper Extremity Deep Vein Thrombosis and Asymptomatic Vein Occlusion in Patients With Transvenous Leads: A Systematic Review and Meta-Analysis

Aims: The presence of transvenous leads for cardiac device therapy may increase the risk of venous thromboembolisms. The epidemiology of these complications has not yet been determined systematically. Therefore, this study aims to determine (I) the incidence of symptomatic upper extremity deep vein thrombosis (UEDVT) and (II) the prevalence of asymptomatic upper extremity vein occlusion in patients with transvenous leads, both after the initial 2 months following lead implantation. Methods: PubMed, EMBASE, and Cochrane Library were searched until March 31, 2020 to identify studies reporting incidence of UEDVT and prevalence of asymptomatic vein occlusion after the initial 2 months after implantation in adult patients with transvenous leads. Incidence per 100 patient years of follow-up (PY) and proportions (%) were calculated to derive pooled estimates of incidence and prevalence. Results: Search and selection yielded 20 and 24 studies reporting on UEDVT and asymptomatic vein occlusion, respectively. The overall pooled incidence of UEDVT was 0.9 (95% CI 0.5–1.4) per 100PY after 2 months after lead implantation. High statistical heterogeneity was present among studies (I2 = 82.4%; P = < 0.001) and only three studies considered to be at low risk of bias. The overall pooled prevalence of asymptomatic upper extremity vein occlusion was 8.6% (95% CI 6.0–11.5) with high heterogeneity (I2 = 81.4%; P = <0.001). Meta-regression analysis showed more leads to be associated with a higher risk of UEDVT. Conclusion: Transvenous leads are an important risk factor for symptomatic UEDVT, which may occur up to multiple years after initial lead implantation. Existing data on UEDVT after lead implantation is mostly of poor quality, which emphasizes the need for high quality prospective research. Asymptomatic vein occlusion is present in a substantial proportion of patients and may complicate any future lead addition. Clinical Trial Registration: (URL: https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42020178136, Identifier: PROSPERO 2020 CRD42020178136).
Development and Psychometric Validation of the Brief Nurses' Practice Environment Scale and Its Relation to Burnout Syndrome and Job Satisfaction: A Study in Spanish Nurses

Introduction: Nursing environment is a vast concept that traditionally has included a wide range of job characteristics and has been related to burnout and job satisfaction. For its measurement, the Practice Environment Scale of the Nursing Work Index (PESNWI) stands out. However, shorter instruments are needed. The purpose of the study is to develop and test the Brief Nurses' Practice Environment (BNPE) Scale. Methods: The BNPE Scale was developed and tested in a sample of 210 Spanish nurses (data collection 2018). Results: Cronbach's alpha was 0.702. The confirmatory factor analysis (CFA), with an excellent fit, offered evidence of internal validity. Regarding validity, the BNPE Scale predicted both burnout and job satisfaction. Finally, evidence pointed out a cutoff score of <12 for low levels of practice environment and a cutoff score of >15 for higher levels in practice environment. Conclusions: The BNPE Scale is a short, easy-to-use measure that could be employed in major batteries assessing the quality of healthcare institutions.
Relationship Between Serum Albumin and Risk of Atrial Fibrillation: A Dose-Response Meta-Analysis

Background: The dose–response association between serum albumin and atrial fibrillation is not well known. This study aims to assess the relationship between albumin and atrial fibrillation and the potential dose–response effect. Methods: Studies reported that the serum albumin and AF were identified by searching the EMBASE, PubMed, and Cochrane Library databases. The potential dose–response effect was performed by using a stage robust error meta-regression. Results: Nine studies were included with a total of 32,130 individuals. Patients with high albumin level were associated with a decreased risk of atrial fibrillation compared with patients with low serum albumin (OR[odds ratio]: 0.62, 95% CI [0.44, 0.89]; I2 = 76%; P = 0.009). In the dose–response analysis, for each 10 g/L increase in serum albumin level, the risk of atrial fibrillation decreased by 36% (95% CI: 0.51–0.81, I2 = 87%, P < 0.001). Furthermore, a significant negative linear relationship between serum albumin and the risk of atrial fibrillation (Pnonlinearity = 0.33) was found. Conclusion: Our dose–response meta-analysis suggests that low serum albumin level is associated with an increased risk of atrial fibrillation. Further studies are needed to explore the effect of induction of elevated serum albumin levels on the prevention of atrial fibrillation.
Activation of Pancreatic Stellate Cells Is Beneficial for Exocrine but Not Endocrine Cell Differentiation in the Developing Human Pancreas

Pancreatic stellate cells (PaSCs) are non-endocrine, mesenchymal-like cells that reside within the peri-pancreatic tissue of the rodent and human pancreas. PaSCs regulate extracellular matrix (ECM) turnover in maintaining the integrity of pancreatic tissue architecture. Although there is evidence indicating that PaSCs are involved in islet cell survival and function, its role in islet cell differentiation during human pancreatic development remains unclear. The present study examines the expression pattern and functional role of PaSCs in islet cell differentiation of the developing human pancreas from late 1st to 2nd trimester of pregnancy. The presence of PaSCs in human pancreata (8–22 weeks of fetal age) was characterized by ultrastructural, immunohistological, quantitative RT-PCR and western blotting approaches. Using human fetal PaSCs derived from pancreata at 14–16 weeks, freshly isolated human fetal islet-epithelial cell clusters (hIECCs) were co-cultured with active or inactive PaSCs in vitro. Ultrastructural and immunofluorescence analysis demonstrated a population of PaSCs near ducts and newly formed islets that appeared to make complex cell-cell dendritic-like contacts. A small subset of PaSCs co-localized with pancreatic progenitor-associated transcription factors (PDX1, SOX9, and NKX6-1). PaSCs were highly proliferative, with significantly higher mRNA and protein levels of PaSC markers (desmin, αSMA) during the 1st trimester of pregnancy compared to the 2nd trimester. Isolated human fetal PaSCs were identified by expression of stellate cell markers and ECM. Suppression of PaSC activation, using all-trans retinoic acid (ATRA), resulted in reduced PaSC proliferation and ECM proteins. Co-culture of hIECCs, directly on PaSCs or indirectly using Millicell® Inserts or using PaSC-conditioned medium, resulted in a reduction the number of insulin+ cells but a significant increase in the number of amylase+ cells. Suppression of PaSC activation or Notch activity during the co-culture resulted in an increase in beta-cell differentiation. This study determined that PaSCs, abundant during the 1st trimester of pancreatic development but decreased in the 2nd trimester, are located near ductal and islet structures. Direct and indirect co-cultures of hIECCs with PaSCs suggest that activation of PaSCs has opposing effects on beta-cell and exocrine cell differentiation during human fetal pancreas development, and that these effects may be dependent on Notch signaling.
Fluoride Exposure and Probabilistic Health Risk Assessment Through Different Agricultural Food Crops From Fluoride Endemic Bankura and Purulia Districts of West Bengal, India

The present study investigates the magnitude of fluoride (F−) contamination in agricultural land soil and food crops from F− endemic regions of Bankura and Purulia districts in West Bengal. Mean fluoride level in agricultural soil was 114 ± 59 mg/kg (n = 41) and 126 ± 65 mg/kg (n = 47) in Bankura and Purulia districts, respectively. Considering the food crops cultivated in Bankura (n = 79) and Purulia (n = 108), the mean fluoride concentration in nonleafy vegetables (18.1 ± 6.51 mg/kg and 15.6 ± 5.93 mg/kg) and leafy vegetables (12.8 ± 2.8 mg/kg and 18.4 ± 6.33 mg/kg) from the two studied districts was comparatively higher than that in the cereal (2 ± 1.05 mg/kg and 2.01 ± 1.01 mg/kg) and pulses (3.35 ± 1.42 mg/kg and 4.82 ± 1.19 mg/kg). The BCF values of fluoride in food crops (n = 27) from Bankura (range: 0.007–0.377) and Purulia (range: 0.005–0.319) were much lower than the optimum value of 1. Estimated daily intake (EDI) of fluoride was the highest for children in both Bankura (EDIcumulative = 0.0291 mg/kg bw/day) and Purulia (EDIcumulative = 0.0326 mg/kg bw/day) among all the studied age groups. The nonleafy vegetables contributed the highest exposure of fluoride (approximately 55.5%) to EDIcumulative among all the food crops. The uncertainty analysis for assessment of probabilistic health risk was carried out for all the studied age groups through hazard index (HI), total hazard index (THI), and lifetime noncarcinogenic risk (HILTNR). However, HI value was found to be <1 for all the age groups resulting in no such kind of potential health risk of fluorosis through consumption of individual food crops, and the trend of THI from all the food crops was found in the order of children > adults > adolescents > teenagers from both districts. The lifetime noncarcinogenic risk (HILTNR) of fluoride with percentile doses from P5 to P95 (exploring the model of Monte Carlo simulation) in all the studied age groups (4–70 years) was found to be >1 indicating that the inhabitants were more vulnerable for their total lifetime period of fluoride exposure through consumption of food crops.
The Influence of Cesarean Section on the Composition and Development of Gut Microbiota During the First 3 Months of Life

The intestinal microbiota has emerged as a critical regulator of growth and development in the early postnatal period of life. Cesarean section (CS) delivery is one of the strongest disrupting factors of the normal colonization process and has been reported as a risk factor for disorders in later life. In this study, we dynamically and longitudinally evaluated the impact of CS on the initial colonization pattern and development of gut microbiota by 16 healthy Chinese infants with fecal samples collected at 9 time points (day 5, day 8, day 11, week 2, week 4, week 6, week 7, month 2, and month 3) during the first 3 months of life. The V3–V4 regions of 16S rRNA gene were analyzed by Illumina sequencing. In comparison with vaginally delivered (VD) infants, infants born by CS showed decreased relative abundance of Bacteroides and Parabacteroides and enrichment of Clostridium_sensu_stricto_1, Enterococcus, Klebsiella, Clostridioides, and Veillonella. Most interestingly, Firmicutes/Bacteroidetes ratio was found to be significantly higher in the CS group than in the VD group from day 5 until month 3. Besides, the results of microbial functions showed that the VD group harbored significantly higher levels of functional genes in vitamin B6 metabolism at day 5, day 8, week 2, week 4, week 6, week 7, month 2, and month 3 and taurine and hypotaurine metabolism at day 5, while the phosphotransferase system and starch and sucrose metabolism involved functional genes were plentiful in the CS group at day 11, week 2, week 4, week 6, week 7, and month 2 and at week 2, week 7, and month 2, respectively. Our results establish a new evidence that CS affected the composition and development of gut microbiota in the first 3 months and provide a novel insight into strategies for CS-related disorders in later life.