Miracle-dz/UniFAR-FTUs huggingface dataset:
The Influence of the North Atlantic Oscillation and East Atlantic Pattern on Drought in British Catchments

Drought events are influenced by a combination of both climatic and local catchment characteristics. In Great Britain the North Atlantic Oscillation (NAO) has long been recognised as the leading mode of climate variability, and studies have also noted the role of the East Atlantic Pattern (EA) as a secondary mode. This study aimed to develop an understanding of the combined influence of the NAO and EA on rainfall distribution and magnitude and the variable nature of meteorological to hydrological drought propagation. Initially, this study explores correlations between teleconnection indices and standardised precipitation and streamflow indices for 291 catchments across Great Britain, before focusing on nine case study catchments for further analysis. For each case study catchment, we use quantile regression and an analysis of drought frequency to explore the combined influence of the NAO and EA on drought conditions. Through a convergence of evidence from these analyses we make three observations. Firstly, in the winter months both the NAO and EA exert an influence on drought conditions, however there is spatial variability in the relative influence of the NAO and EA; the NAO has a stronger influence in the north-west, whilst the EA has a stronger influence in the southern and central regions. Secondly, in the summer months, less distinctive spatial differences were found, with higher probability of drought conditions under NAO+ phases, which however can be enhanced or moderated by the EA. Finally, as a result of catchment characteristics there is spatio-temporal variability in the propagation of meteorological to hydrological drought. Our findings suggest that by considering the NAO and EA in combination, we can better describe climate and drought variability. We conclude by noting the potential implications our study has on the role of monthly teleconnection forecasts in water management decision making in Great Britain, and acknowledge the current limitations associated with incorporating such understanding.
Breath Tools: A Synthesis of Evidence-Based Breathing Strategies to Enhance Human Running

Running is among the most popular sporting hobbies and often chosen specifically for intrinsic psychological benefits. However, up to 40% of runners may experience exercise-induced dyspnoea as a result of cascading physiological phenomena, possibly causing negative psychological states or barriers to participation. Breathing techniques such as slow, deep breathing have proven benefits at rest, but it is unclear if they can be used during exercise to address respiratory limitations or improve performance. While direct experimental evidence is limited, diverse findings from exercise physiology and sports science combined with anecdotal knowledge from Yoga, meditation, and breathwork suggest that many aspects of breathing could be improved via purposeful strategies. Hence, we sought to synthesize these disparate sources to create a new theoretical framework called “Breath Tools” proposing breathing strategies for use during running to improve tolerance, performance, and lower barriers to long-term enjoyment.
Adenosinergic Pathway and Linked Suppression: Two Critical Suppressive Mechanisms of Human Donor Antigen Specific Regulatory T Cell Lines Expanded Post Transplant

Regulatory T cells are an important component of an immune response shaping the overall behavior to potential antigens including alloantigens. Multiple mechanisms have been shown to contribute towards developing and sustaining a immunological regulatory response. One of the described contact dependent suppressive mechanisms regulatory cells have been shown to utilize is through the production of adenosine from extracellular ATP mediated by CD39 and CD73. In this study we demonstrate that the adenosinergic pathway plays a major role in the suppressive/regulatory effects antigen specific regulatory T cell enriched lines (ASTRLs) that have been of expanded ex vivo from stable kidney transplant patients. We have previously shown that these ASTRL cells are capable of suppressing alloimmune responses in vitro and significantly prolonging allograft survival in an animal model of kidney transplantation. For this study nineteen ASTRLs were expanded from 17 kidney transplant patients by repeated stimulation of recipient peripheral blood mononuclear cells with donor specific HLA-DR peptides. All 19 ASTRLs showed upregulation of numerous markers associated with regulatory cells and were able to inhibit donor antigen specific T cell proliferation in a dose dependent fashion. ASTRLs suppressed indirect and direct alloimmune responses compatible with our previous animal study findings. Upregulation of both CD39 and CD73 was observed post expansion and ASTRLs demonstrated extracellular hydrolysis of ATP, indicating functionality of the upregulated proteins. We also showed that inhibition of the adenosinergic pathway using inhibitors of CD39 resulted in abrogation of suppression and increased antigen specific T cell proliferation. This demonstrates that the main mechanism of action of the suppressive activity donor peptide driven ASTRLs generated from kidney transplant patients is the adenosinergic pathway. Furthermore this suggests the possibility that combining infusion of Tregs with other treatments, such as adenosine receptor agonists or increasing CD39 expression in the grafts may further enhance a regulatory response to the allograft and possibly achieve transplantation tolerance.
Roles of Insect Oenocytes in Physiology and Their Relevance to Human Metabolic Diseases

Oenocytes are large secretory cells present in the abdomen of insects known to synthesize very-long-chain fatty acids to produce hydrocarbons and pheromones that mediate courtship behavior in adult flies. In recent years, oenocytes have been implicated in the regulation of energy metabolism. These hepatocyte-like cells accumulate lipid droplets under starvation and can non-autonomously regulate tracheal waterproofing and adipocyte lipid composition. Here, we summarize evidence, mostly from Drosophila, establishing that oenocytes perform liver-like functions. We also compare the functional differences in oenocytes and the fat body, another lipid storage tissue which also performs liver-like functions. Lastly, we examine signaling pathways that regulate oenocyte metabolism derived from other metabolic tissues, as well as oenocyte-derived signals that regulate energy homeostasis.
Capsaicin Ameliorates the Loosening of Mitochondria-Associated Endoplasmic Reticulum Membranes and Improves Cognitive Function in Rats With Chronic Cerebral Hypoperfusion

Based on accumulating evidence, vascular factors contribute to cognitive decline and dementia. Mitochondrial dysfunction is the core pathophysiological mechanism. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are subcellular structures that physically and biologically connect mitochondria with the endoplasmic reticulum (ER) and regulate multiple functions ranging from calcium transfer to mitochondrial dynamics and bioenergetics. MAMs dysfunction has been speculated to be a key factor contributing to the pathogenesis of cognitive disorders and a new therapeutic target. However, the alteration of MAMs in vascular cognitive impairment remains to be revealed. Capsaicin, a specific agonist known to activated the transient receptor potential vanilloid type 1 (TRPV1), is involved in hippocampal synaptic plasticity and memory, but the detailed mechanism is still unclear. In this study, chronic cerebral hypoperfusion (CCH) model rats were created by bilateral common carotid artery occlusion (BCCAO), which is a widely used model to study vascular dementia. We observed that CCH rats showed obvious cognitive deficits, and ER-mitochondria contacts were loosener with lower expression of mitofusin2 (MFN2), a key protein connecting MAMs, in the hippocampal CA1 region, compared to the sham group. After capsaicin treatment for 12 weeks, we found that cognitive deficits induced by CCH were significantly alleviated and loosened ER-mitochondrial interactions were obviously improved. In conclusion, the findings of this study highlight that MAMs may contribute to the pathogenesis of cognitive impairment induced by CCH, and our new evidence that capsaicin improves cognitive function highlights a novel opportunity for drug discovery.
The Value of Shear Wave Elastography in the Diagnosis of Breast Cancer Axillary Lymph Node Metastasis and Its Correlation With Molecular Classification of Breast Masses

Objective To explore the diagnostic value of shear wave elastography examination (SWE) on axillary node metastasis (ANM) in breast cancer, this study aimed to evaluate the correlation between the SWE features and different molecular types of breast cancer, and to check the elastic modulus differences among the molecular types. Methods Breast cancer patients from November 2020 to December 2021 were subjected to both conventional ultrasonic examination (CUE) and SWE before ultrasound-guided percutaneous biopsy or axillary lymph node dissection (ALND). We used the pathological results as the gold standard to draw the receiver operating characteristic (ROC) curve. Results SWE outperforms CUE, but their conjunctive use is the best option. No significant correlation was found between the elastic modulus values and the molecular types of breast cancer. Conclusion SWE can be used as an routine auxiliary method of CUE for ANM.
L-Methylfolate in Antidepressant Non-responders: The Impact of Body Weight and Inflammation

This summary provides context for the role of L-methylfolate (LMF) in treating antidepressant non-responders. Bidirectional relationships have been observed between obesity and/or inflammation and depression. Studies have shown an increased prevalence of depression among patients with elevated body mass index and/or chronic inflammation and an increased risk of becoming obese and experiencing chronic inflammation in those with depression. These relationships can negatively affect the pathophysiology of depression. Elevated cytokine levels have been found to be among the factors that correlate with poor antidepressant treatment responsiveness. Low baseline neurotransmitter levels (e.g., serotonin) can also be associated with reduced effectiveness of commonly used antidepressants [e.g., selective serotonin reuptake inhibitors (SSRIs)]. LMF is an approved nutritional adjunctive antidepressant therapy that increases central neurotransmitter levels and thereby improves the effectiveness of antidepressant therapy. LMF can increase clinical response when used adjunctively in patients with major depressive disorder (MDD) and who are SSRI-resistant. In 2 randomized controlled trials, the pooled results showed increased response rates (32.3 vs. 14.6%; P = 0.04) as measured by a ≥50% reduction or final score ≤ 7 on the Hamilton Depression Rating Scale (HAM-D) and greater mean HAM-D reductions (−5.6 vs. −3.0; P = 0.05) when LMF was added to an SSRI compared with an SSRI plus placebo. Additionally, LMF has demonstrated effectiveness in real-world studies, with 67.9% of patients responding to therapy, using the 9-item Patient Health Questionnaire (P < 0.001). Post-hoc analyses found that patients with inflammation and/or obesity responded better to adjunctive LMF therapy compared with the overall sample (mean HAM-D reduction: −2.74 vs. +0.99).
Reconstruction of Large Full-Thickness Abdominal Wall Defects Using a Free Functional Latissimus Dorsi Muscle

Introduction The large full-thickness abdominal wall defect has to be treated by considering anatomical and functional requirements. The abdominal wall must regain total physiological function, which means that the full thickness abdominal wall defect must be reconstructed anatomically, not only according to the anatomical requirements but also maintaining the functional dynamic voluntary movement. Defects in the abdominal wall alter respiratory mechanics and can impair the diaphragm function. Additionally, muscles of the anterolateral abdominal wall increase the stability of the lumbar region of the vertebral column by tensing the thoracolumbar fascia and by increasing intraabdominal pressure. Materials and Methods The timing and method of reconstruction must be chosen depending upon the etiology of the defect. Severe traumatic injuries, abdominal wall infections, necrotizing soft tissue loss, or sepsis needs to undergo staged reconstruction following adequate debridement to control the infectious process, establish the zone of injury, and for proper treatment of intraabdominal pathology, thereby achieving temporary primary closure using split-thickness skin grafting to the viscera. At the time of definitive reconstruction, deep skin graft dermabrasion give us a facial-like layer with adequate strength to stabilize the static abdominal wall. This dermal layer is supported by free functional (innervated) latissimus dorsi muscle (fLDM), giving full anatomical coverage and functional stability. After oncologic resections full-thickness abdominal wall reconstruction was performed immediately with a combination of fLDM flaps and meshes. Results A total of 14 patients underwent abdominal wall reconstruction using the fLDM flap. Staged reconstruction was applied in 8 cases. In the remaining six cases, two had no mesh support, three had synthetic mesh, and one had a fascial graft, which were covered with fLDM flap. There were no free flaps failure. One flap revision due to venous anastomosis thrombosis was performed. Donor site seromas occurred in 5 cases and were treated with punction and direct doxycycline injection. Electromyographic testing postoperatively confirmed reinnervation of transplanted LDM. Conclusion Using fLDM as a definitive solution, we are not only able to repair soft tissue defects, but also reconstruct voluntary contractility and dynamic natural functional abdominal wall. Transplanted LDM offers enough contractile capacity and strength to replace the function of the missing abdominal wall muscles.
MicroRNA-138 Abates Fibroblast Motility With Effect on Invasion of Adjacent Cancer Cells

Background Recent studies have shown aberrant expression of micro-RNAs in cancer-associated fibroblasts (CAFs). This study aimed to investigate miR-138 dysregulation in CAFs in oral squamous cell carcinoma (OSCC) and its effects on their phenotype and invasion of adjacent OSCC cells. Methods Expression of miR-138 was first investigated in OSCC lesions (n = 53) and OSCC-derived CAFs (n = 15). MiR-138 mimics and inhibitors were used to functionally investigate the role of miR-138 on CAF phenotype and the resulting change in their ability to support OSCC invasion. Results Expression of miR-138 showed marked heterogeneity in both OSCC tissues and cultured fibroblasts. Ectopic miR-138 expression reduced fibroblasts’ motility and collagen contraction ability and suppressed invasion of suprajacent OSCC cells, while its inhibition resulted in the opposite outcome. Transcript and protein examination after modulation of miR-138 expression showed changes in CAF phenotype-specific molecules, focal adhesion kinase axis, and TGFβ1 signaling pathway. Conclusions Despite its heterogeneous expression, miR-138 in OSCC-derived CAFs exhibits a tumor-suppressive function.
Influence of E-Liquid Humectants, Nicotine, and Flavorings on Aerosol Particle Size Distribution and Implications for Modeling Respiratory Deposition

Electronic cigarette, or vaping, products are used to heat an e-liquid to form an aerosol (liquid droplets suspended in gas) that the user inhales; a portion of this aerosol deposits in their respiratory tract and the remainder is exhaled, thereby potentially creating opportunity for secondhand exposure to bystanders (e.g., in homes, automobiles, and workplaces). Particle size, a critical factor in respiratory deposition (and therefore potential for secondhand exposure), could be influenced by e-liquid composition. Hence, the purposes of this study were to (1) test the influence of laboratory-prepared e-liquid composition [ratio of propylene glycol (PG) to vegetable glycerin (VG) humectants, nicotine, and flavorings] on particle size distribution and (2) model respiratory dosimetry. All e-liquids were aerosolized using a second-generation reference e-cigarette. We measured particle size distribution based on mass using a low-flow cascade impactor (LFCI) and size distribution based on number using real-time mobility sizers. Mass median aerodynamic diameters (MMADs) of aerosol from e-liquids that contained only humectants were significantly larger compared with e-liquids that contained flavorings or nicotine (p = 0.005). Humectant ratio significantly influenced MMADs; all aerosols from e-liquids prepared with 70:30 PG:VG were significantly larger compared with e-liquids prepared with 30:70 PG:VG (p = 0.017). In contrast to the LFCI approach, the high dilution and sampling flow rate of a fast mobility particle sizer strongly influenced particle size measurements (i.e., all calculated MMAD values were < 75 nm). Dosimetry modeling using LFCI data indicated that a portion of inhaled particles will deposit throughout the respiratory tract, though statistical differences in aerosol MMADs among e-liquid formulations did not translate into large differences in deposition estimates. A portion of inhaled aerosol will be exhaled and could be a source for secondhand exposure. Use of laboratory-prepared e-liquids and a reference e-cigarette to standardize aerosol generation and a LFCI to measure particle size distribution without dilution represents an improved method to characterize physical properties of volatile aerosol particles and permitted determination of MMAD values more representative of e-cigarette aerosol in situ, which in turn, can help to improve dose modeling for users and bystanders.
Functional Diversities of Regulatory T Cells in the Context of Cancer Immunotherapy

Regulatory T cells (Tregs) are a subset of CD4+ T cells with their immunosuppressive activities to block abnormal or excessive immune responses to self and non-autoantigens. Tregs express the transcription factor Foxp3, maintain the immune homeostasis, and prevent the initiation of anti-tumor immune effects in various ways as their mechanisms to modulate tumor development. Recognition of different phenotypes and functions of intratumoral Tregs has offered the possibilities to develop therapeutic strategies by selectively targeting Tregs in cancers with the aim of alleviating their immunosuppressive activities from anti-tumor immune responses. Several Treg-based immunotherapeutic approaches have emerged to target cytotoxic T lymphocyte antigen-4, glucocorticoid-induced tumor necrosis factor receptor, CD25, indoleamine-2, 3-dioxygenase-1, and cytokines. These immunotherapies have yielded encouraging outcomes from preclinical studies and early-phase clinical trials. Further, dual therapy or combined therapy has been approved to be better choices than single immunotherapy, radiotherapy, or chemotherapy. In this short review article, we discuss our current understanding of the immunologic characteristics of Tregs, including Treg differentiation, development, therapeutic efficacy, and future potential of Treg-related therapies among the general cancer therapy.
The Prognostic Significance and Gene Expression Characteristics of Gastric Signet-Ring Cell Carcinoma: A Study Based on the SEER and TCGA Databases

Purpose This study is based on the Surveillance, Epidemiology, and End Results (SEER) program to explore the prognostic differences between signet-ring cell carcinoma (SRC) and intestinal-type gastric carcinoma (ITGC). This study is also based on gene sequencing data from The Cancer Genome Atlas (TCGA) to identify unique genetic contributions to the prognostic differences between the two subtypes of gastric cancer. Patients and Methods The clinical data were based on the SEER database from 2004 to 2015. Kaplan–Meier (KM) curves were used to compare 5-year overall survival (OS), and Cox regression was used for univariate and multivariate analyses. Gene expression profiles were obtained from TCGA database, and differentially expressed genes (DEGs) were screened. Functional enrichment analysis, protein interaction and survival analysis will be further carried out. Genes of interest were verified by the Human Protein Atlas, immunohistochemistry, and encyclopedia of Cancer Cell Lines (CCLE). The relationship between genes of interest and immune cell infiltration was also analyzed by Tumor Immune Estimation Resource (TIMER). Results Compared with ITGC patients, SRC patients were more likely to be female, tended to be younger, and have a greater tumor distribution in the middle and lower stomach (p < 0.01). SRCs showed a significantly better prognosis than ITGCs (p < 0.01) in early gastric cancer (EGC), while the prognosis of SRCs was significantly worse than ITGCs (p < 0.05) in advanced gastric cancer (AGC). A total of 256 DEGs were screened in SRCs compared to ITGCs, and the enrichment analysis and protein interactions revealed that differential genes were mainly related to extracellular matrix organization. Thrombospondin1 (THBS1) and serpin peptidase inhibitor, clade E, member 1 (SERPINE1) are significantly differentially expressed between SRC and ITGC, which has been preliminarily verified by immunohistochemistry and open-source databases. THBS1 and SERPINE1 are also associated with multiple immune cell infiltrates in gastric cancer. Conclusions There were significant differences in the clinicopathological features and prognosis between SRC and ITGC. These results suggest that SRC and ITGC may be two distinct types of tumors with different pathogeneses. We found many codifferentially expressed genes and important pathways between SRC and ITGC. THBS1 and SERPINE1 were significantly differentially expressed in the two types of gastric cancer, and may have potentially important functions.
Modified Intraperitoneal Chemotherapy Without Bevacizumab as a First-Line Therapy for Newly Diagnosed Advanced Epithelial Ovarian Cancer-Two Centers Experiences

Objectives To evaluate whether the modified intraperitoneal plus intravenous chemotherapy regimen as a first-line therapy for advanced epithelial ovarian cancer (EOC) in China can be well-tolerated or confer any potential benefit on survival. Methods We evaluated the outcomes of women with newly diagnosed advanced-stage III-IV EOC treated with optimal cytoreductive surgery (<1 cm) and subsequent intraperitoneal plus intravenous chemotherapy or intravenous chemotherapy from January 2005 to December 2017 at two Gynecologic Oncology Centers in China. Kaplan-Meier survival analysis and Cox regression multivariate analysis models were performed to determine the toxicities and survival outcomes. Results A total of 463 patients with stage III-IV EOC were enrolled. According to the propensity scores (1:2), 85 patients who received intraperitoneal plus intravenous chemotherapy (group A) were matched to 170 patients who received intravenous chemotherapy (group B). The median follow-up time was 41 months (range 6–155 months). However, there was no statistically significant difference in the median progression-free survival (PFS) (20 vs. 22 months, P = 0.351) or 3-year overall survival (OS) rate (80 vs. 78%, P = 0.749) between the two groups. R0 primary cytoreductive surgery was the only factor related to PFS (P = 0.028) and OS (P = 0.005) by Cox regression analysis. The incidence of grade 3/4 adverse events did not significantly differ between the two groups. Conclusion The efficacy of intraperitoneal chemotherapy mainly comes from the intraperitoneal drug dose intensity and cumulative dose. High-efficiency and low-toxicity intraperitoneal chemotherapy regimens still need to be found and validated.