Miracle-dz/UniFAR-FTUs huggingface dataset:
Cortisol and Phosphate Homeostasis: Cushing’s Syndrome Is Associated With Reversible Hypophosphatemia

Objectives The influence of hypercortisolism on phosphate homeostasis is relatively unknown. A few previous studies have reported on patients with Cushing’s syndrome (CS) with hypophosphatemia in whom serum phosphate normalized after initiation of treatment for CS. We aimed to investigate the prevalence of hypophosphatemia in CS, the association between the degree of hypercortisolism and serum phosphate and the change in serum phosphate after remission of CS. We compared the prevalence of hypophosphatemia in CS with the prevalence in the population-based Rotterdam Study (RS). Methods Patients diagnosed with CS and treated at the Department of Endocrinology of Erasmus MC in the period of 2002-2020 were included and data was collected on age at diagnosis, sex, serum phosphate, calcium and potassium levels, kidney function and BMI. Using multivariate linear regression, we analyzed the association between 24h urinary free cortisol excretion (UFC) and serum phosphate. Changes in serum phosphate and covariates were tested with a repeated measurement ANOVA, using mean levels of laboratory values for the periods before remission, and 0-14 days and 15-180 days after remission. Results Hypophosphatemia before treatment was present in 16% of the 99 CS patients with data on serum phosphate, 24h UFC and covariates. In comparison, the prevalence of hypophosphatemia in RS was 2.0-4.2%. Linear regression showed a negative association between the level of UFC and serum phosphate at diagnosis, which remained significant after adjusting for covariates [β -0.002 (95%CI -0.004; -0.0004), p=0.021]. A subset of 24 patients had additional phosphate measurements at 0-14 days and 15-180 days after remission. In this subgroup, serum phosphate significantly increased from 1.03 ± 0.17 mmol/L prior to remission to 1.22 ± 0.25 mmol/L 15-180 days after remission (p = 0.008). BMI decreased after remission [-1.1 kg/m2, (95%CI -2.09 to -0.07), p=0.037]. Other covariates did not show an equivalent change over time. Conclusion In this retrospective study, we found that 16% of patients with CS had hypophosphatemia. Moreover, serum phosphate was related to the level of cortisoluria and increased after remission of CS. Potential underlying mechanisms related to urinary phosphate excretion and possibly involving FGF23, BMI and parathyroid hormone levels should be further explored.
Moisture Changes in the Northern Xinjiang Basin Over the Past 2400 years as Documented in Pollen Records of Jili Lake

Regional humidity is important for terrestrial ecosystem development, while it differs from region to region in inland Asia, knowledge of past moisture changes in the lower basin of northern Xinjiang remainly largely unclear. Based on a pollen record from Jili Lake, the Artemisia/(Amaranthaceae + Ephedra) (Ar/(Am + E)) ratio, as an index of regional humidity, has recorded four relatively dry phases: 1) 400 BCE to 1 CE, 2) the Roman Warm Period (RWP; c. 1–400 CE), 3) the Medieval Warm Period (MWP; c. 850–1200 CE) and 4) the Current Warm Period (CWP; since 1850 CE). In contrast, the Dark Age Cold Period (DACP; c. 400–850 CE) and the Little Ice Age (LIA; c. 1200–1850 CE) were relatively wet. Lower lake levels in a relatively humid climate background indicated by higher aquatic pollen (Typha and Sparganium) after c. 1700 CE are likely the result of intensified irrigation for agriculture in the catchment as documented in historical records. The pollen Ar/(Am + E) ratio also recorded a millennial-scale wetting trend from 1 CE to 1550 CE which is concomitant with a long-term cooling recorded in the Northern Hemisphere.
Molecular Characterization Analysis of Thalassemia and Hemoglobinopathy in Quanzhou, Southeast China: A Large-Scale Retrospective Study

Background: There are limited reports available on investigations into the molecular spectrum of thalassemia and hemoglobinopathy in Fujian province, Southeast China. Here, we aim to reveal the spectrum of the thalassemia mutation and hemoglobinopathy in Quanzhou prefecture, Fujian province. Methods: We collected data from a total of 17,407 subjects with the thalassemia trait in Quanzhou prefecture. Gap-PCR, DNA reverse dot blot hybridization, and DNA sequencing were utilized for common and rare thalassemia gene testing. Results: In our study, we identified 7,085 subjects who were carrying thalassemia mutations, representing a detection rate of 40.70% (7,085/17,407). Among them, 13 different α-thalassemia gene mutations were detected, with the most common mutation being –SEA (69.01%), followed by –α3. 7 (21.34%) and –α4. 2 (3.96%). We also discovered 26 β-thalassemia gene mutations, with the mutations of IVS-II-654 (C > T) (36.28%) and CD41/42(–TCTT) (29.16%) being the most prevalent. Besides, a variety of rare thalassemia variants were identified. Among them, the –FIL, βMalay, βIVS–I–130, and βIVS–II–672 mutations were identified in Fujian province for the first time. Additionally, we detected 78 cases of hemoglobinopathies, of which Hb Owari was the first reported case in Fujian province and Hb Miyashiro was the first case identified in the Chinese population. Conclusion: Our study indicates that there is a diverse range of thalassemia mutations, and it also reveals the mutation spectrum of rare thalassemia and hemoglobinopathies in Quanzhou, Fujian province. It provides valuable data for the prevention and control of thalassemia in Southeast China.
Synbiotics Supplements Lower the Risk of Hand, Foot, and Mouth Disease in Children, Potentially by Providing Resistance to Gut Microbiota Dysbiosis

Background Hand, foot and mouth disease (HFMD) is an acute enterovirus-induced disease. Gut microbiota dysbiosis has been identified as a factor that plays an important role in enteral virus infection, but the gut microbiota profile in hand, foot and mouth disease has rarely been studied in a large population. Methods A total of 749 children (HFMD: n = 262, healthy control: n = 487) aged 2 to 7 years were recruited from hospitals and communities in the period from May to July, 2017. Clinical and demographical information was collected by trained personnel, and fecal samples were collected and processed for 16S ribosomal RNA(rRNA) gene sequencing. Results We observed a significant alteration in the microbiota profile of children with HFMD compared with that of control children. Patients with enteroviruses A71(EV71) positive had more dysbiotic gut microbiota than those with coxsackievirus A16 (CAV16) positive. We found that Prevotella and Streptococcus were enriched in children with HFMD, whereas beneficial bacteria, including Bifidobacterium and Faecalibacterium, were depleted. Children with synbiotics supplements had lower risk of HFMD and we observed that the gut microbiota of HFMD patients who were administered synbiotics exhibited potential resistance to the dysbiosis detected in HFMD. Conclusions This study suggested that the gut microbiota of patients with hand, foot and mouth disease exhibits dysbiosis and that synbiotics supplements potentially helps maintain the homeostasis of the gut flora.
Patterns of Tyrosine Kinase Inhibitor Utilization in Newly Treated Patients With Chronic Myeloid Leukemia: An Exhaustive Population-Based Study in France

We analyzed demographic characteristics, comorbidities and patterns of treatment with tyrosine kinase inhibitors (TKIs) in a cohort of 3,633 incident cases of chronic myeloid leukemia (CML) identified across France from 1 January 2011 to 31 December 2014. Patients were identified through a specific algorithm in the French Healthcare Data System and were followed up 12 months after inclusion in the cohort. The estimated incidence rate of CML for this period in France was 1.37 per 100,000 person-years (95% Confidence Interval 1.36-1.38) and was higher in men, with a peak at age 75-79 years. At baseline, the median age of the cohort was 60 years (Inter Quartile Range 47-71), the Male/Female ratio was 1.2, and 25% presented with another comorbidity. Imatinib was the first-line TKI for 77.6% of the patients, followed by nilotinib (18.3%) and dasatinib (4.1%). Twelve months after initiation, 86% of the patients remained on the same TKI, 13% switched to another TKI and 1% received subsequently three different TKIs. During the follow-up, 23% discontinued and 52% suspended the TKI. Patients received a mean of 16.7 (Standard Deviation (SD) 9.6) medications over the first year of follow-up, and a mean of 2.7 (SD 2.3) concomitant medications on the day of first TKI prescription: 24.4% of the patients received allopurinol, 6.4% proton pump inhibitors (PPI) and 6.5% antihypertensive agents. When treatment with TKI was initiated, incident CML patients presented with comorbidities and polypharmacy, which merits attention because of the persistent use of these concomitant drugs and the potential increased risk of drug-drug interactions.
High Abdominal Perfusion Pressure Using Umbilical Cord Flap in the Management of Gastroschisis

Background: Gastroschisis management remains a controversy. Most surgeons prefer reduction and fascial closure. Others advise staged reduction to avoid a sudden rise in intra-abdominal pressure (IAP). This study aims to evaluate the feasibility of using the umbilical cord as a flap (without skin on the top) for tension-free repair of gastroschisis. Methods: In a prospective study of neonates with gastroschisis repaired between January 2018 to October 2020 in Tanta University Hospital, we used the umbilical cord as a flap after the evacuation of all its blood vessels and suturing the edges of the cord with the skin edges of the defect. They were guided by monitoring abdominal perfusion pressure (APP), peak inspiratory pressure (PIP), central venous pressure (CVP), and urine output during 24 and 48 h postoperatively. The umbilical cord flap is used for tension-free closure of gastroschisis if PIP > 24 mmHg, IAP > 20 cmH2O (15 mmHg), APP <50 mmHg, and CVP > 15cmH2O. Results: In 20 cases that had gastroschisis with a median age of 24 h, we applied the umbilical cord flap in all cases and then purse string (Prolene Zero) with daily tightening till complete closure in seven cases, secondary suturing after 10 days in four cases, and leaving skin creeping until complete closure in nine cases. During the trials of closure, the range of APP was 49–52 mmHg. The range of IAP (IVP) was 15–20 cmH2O (11–15 mmHg), the range of PIP was 22–25 cmH2O, the range of CVP was 13–15 cmH2O, and the range of urine output was 1–1.5 ml/kg/h. Conclusion: The umbilical cord flap is an easy, feasible, and cheap method for tension-free closure of gastroschisis with limiting the PIP ≤ 24 mmHg, IAP ≤ 20 cmH2O (15 mmHg), APP > 50 mmHg, and CVP ≤ 15cmH2O.
An Experimental and Comparative Performance Evaluation of a Hybrid Photovoltaic-Thermoelectric System

The majority of incident solar irradiance causes thermalization in photovoltaic (PV) cells, attenuating their efficiency. In order to use solar energy on a large scale and reduce carbon emissions, their efficiency must be enhanced. Effective thermal management can be utilized to generate additional electrical power while simultaneously improving photovoltaic efficiency. In this work, an experimental model of a hybrid photovoltaic-thermoelectric generation (PV-TEG) system is developed. Ten bismuth telluride-based thermoelectric modules are attached to the rear side of a 10 W polycrystalline silicon-based photovoltaic module in order to recover and transform waste thermal energy to usable electrical energy, ultimately cooling the PV cells. The experiment was then carried out for 10 days in Lahore, Pakistan, on both a simple PV module and a hybrid PV-TEG system. The findings revealed that a hybrid system has boosted PV module output power and conversion efficiency. The operating temperature of the PV module in the hybrid system is reduced by 5.5%, from 55°C to 52°C. Due to a drop in temperature and the addition of some recovered energy by thermoelectric modules, the total output power and conversion efficiency of the system increased. The hybrid system’s cumulative output power increased by 19% from 8.78 to 10.84 W, compared to the simple PV system. Also, the efficiency of the hybrid PV-TEG system increased from 11.6 to 14%, which is an increase of 17% overall. The results of this research could provide consideration for designing commercial hybrid PV-TEG systems.
Downregulation of Barley Regulator of Telomere Elongation Helicase 1 Alters the Distribution of Meiotic Crossovers

Programmed meiotic DNA double-strand breaks (DSBs), necessary for proper chromosomal segregation and viable gamete formation, are repaired by homologous recombination (HR) as crossovers (COs) or non-crossovers (NCOs). The mechanisms regulating the number and distribution of COs are still poorly understood. The regulator of telomere elongation helicase 1 (RTEL1) DNA helicase was previously shown to enforce the number of meiotic COs in Caenorhabditis elegans but its function in plants has been studied only in the vegetative phase. Here, we characterised barley RTEL1 gene structure and expression using RNA-seq data previously obtained from vegetative and reproductive organs and tissues. Using RNAi, we downregulated RTEL1 expression specifically in reproductive tissues and analysed its impact on recombination using a barley 50k iSelect SNP Array. Unlike in C. elegans, in a population segregating for RTEL1 downregulated by RNAi, high resolution genome-wide genetic analysis revealed a significant increase of COs at distal chromosomal regions of barley without a change in their total number. Our data reveal the important role of RTEL1 helicase in plant meiosis and control of recombination.
MMS22L Expression as a Predictive Biomarker for the Efficacy of Neoadjuvant Chemoradiotherapy in Oesophageal Squamous Cell Carcinoma

Long-term survival in oesophageal squamous cell carcinoma (ESCC) is related with pathological response after neoadjuvant chemoradiotherapy (NCRT) followed by surgery. However, effective biomarkers to predict the pathologic response are still lacking. Therefore, a systematic analysis focusing on genes associated with the efficacy of chemoradiotherapy in ESCC will provide valuable insights into the regulation of molecular processes. By screening publications deposited in PubMed, we collected genes associated with the efficacy of chemoradiotherapy. A specific subnetwork was constructed using the Steiner minimum tree algorithm. Survival analysis in Kaplan-Meier Plotter online resources was performed to explore the relationship between gene mRNA expression and the prognosis of patients with ESCC. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemical staining (IHC) were used to evaluate the expression of key genes in cell lines and human samples. The areas under the receiver operating characteristic (ROC) curves (AUCs) were used to describe performance and accuracy. Transwell assays assessed cell migration, and cell viability was detected using the Cytotoxicity Assay. Finally, we identified 101 genes associated with efficacy of chemoradiotherapy. Additionally, specific molecular networks included some potential related genes, such as CUL3, MUC13, MMS22L, MME, UBC, VAPA, CYP1B1, and UGDH. The MMS22L mRNA expression level showed the most significant association with the ESCC patient outcome (p < 0.01). Furthermore, MMS22L was downregulated at both the mRNA (p < 0.001) and protein levels in tumour tissues compared with that in normal tissues. Lymph node metastasis was significantly associated with low MMS22L expression (p < 0.01). MMS22L levels were inversely correlated with the NCRT response in ESCC (p < 0.01). The resulting area under the ROC curve was 0.847 (95% CI: 0.7232 to 0.9703; p < 0.01). In conclusion, low expression of MMS22L is associated with poor response to NCRT, worse survival, lymph node metastasis, and enhanced migration of tumour cells in ESCC.
Reflections on Neurofeminism and Intersectionality Using Insights From Psychology

Intersectionality contends that sex/gender is constituted of and with other social categories, and that the social structures giving rise to inequality should be addressed in research. This is a powerful and important perspective from which to investigate the processes and consequences of social group memberships, one which has been overlooked by most neuroscientific research. In particular, neurofeminism, a field of critical neuroscience that challenges neuroscientific assumptions, methods and interpretations of data that reinforce sexism, has ignored intersectionality to date. In contrast, research in the field of psychology has been engaging with intersectionality for more than a decade. In reflecting on how intersectionality has advanced feminist research in psychology, this paper provides a critical analysis of potential novel research avenues for neurofeminism. We identify three main research themes guided by intersectionality. The first theme involves research centered on understanding the socio-structural causes of health inequalities experienced by individuals with intersecting marginalized social identities; the second concerns research addressing the psychological processing of social group memberships that underlies the enactment of systemic discriminatory practices; and the third theme comprises intersectionality research that aims to challenge psychological epistemology. Drawing parallels between the fields of psychology and neuroscience, we explore the potential benefits and risks of advancing an intersectionality-informed neurofeminism.
Efficacy and Safety of Tumor Treating Fields (TTFields) in Elderly Patients with Newly Diagnosed Glioblastoma: Subgroup Analysis of the Phase 3 EF-14 Clinical Trial

Background Understudied elderly patients comprise a large segment of high-risk patients with glioblastoma (GBM) that are challenging to treat. Tumor Treating Fields (TTFields) is a locoregional, noninvasive, antimitotic therapy delivering low-intensity, intermediate-frequency alternating electric fields to the tumor. In the phase 3 EF-14 clinical trial, TTFields (200 kHz) improved median progression-free survival (PFS) and median overall survival (OS) in patients with newly diagnosed GBM (ndGBM) when added concomitantly to maintenance temozolomide (TMZ). This EF-14 subgroup analysis evaluated the safety and efficacy of TTFields in elderly patients. Methods All 134 patients who are ≥65 years of age were included (TTFields/TMZ combination, n=89; TMZ monotherapy, n=45; 2:1 ratio of randomization). PFS and OS were analyzed using Kaplan–Meier methodology (α=0.05). Health-related quality-of-life (HRQoL) was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire QLQ-C30 supplemented with the brain tumor module (QLQ-BN20). Adverse events (AEs) were evaluated using Common Terminology Criteria for AEs (CTCAE) v4.0. Results The PFS was 6.5 months in patients randomized to the treatment group with TTFields/TMZ combination versus 3.9 months in patients treated with TMZ monotherapy (HR, 0.47; 95% CI, 0.30–0.74; PP=0.0236). The OS was 17.4 months in patients treated with TTFields/TMZ combination versus 13.7 months in patients treated with TMZ monotherapy (HR, 0.51; 95% CI, 0.33–0.77; PP=0.0204). Annual survival rates with TTFields/TMZ versus TMZ monotherapy were 39% (95% CI, 29–50%) versus 27% (95% CI, 15–41%; P=0.072) at 2 years, 19% (95% CI, 11–29%) versus 11% (95% CI, 4–23%; P=0.135) at 3 years, and 15% (95% CI, 7–25%) versus 0% at 5 years, respectively. There were no significant differences between groups in the preselected items of HRQoL assessment. Grade ≥3 systemic AEs were 46% in the TTFields/TMZ group versus 40% in the TMZ monotherapy group, without statistically significant difference between the two groups. The only TTFields-related AEs were reversible scalp skin reactions, with grades 1–2 and grade 3 skin reactions reported by 51% and 2% of patients, respectively. Conclusions Combining TTFields with maintenance TMZ significantly improved PFS and OS in elderly patients with ndGBM in the phase 3 EF-14 clinical trial, without significant increases in systemic toxicity or negatively affecting patient HRQoL. TTFields-related skin AEs were low-grade and manageable. Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT00916409, identifier: NCT00916409.
Diagnostic Vaccination in Clinical Practice

Testing the antibody response to vaccination (diagnostic vaccination) is crucial in the clinical evaluation of primary immunodeficiency diseases. Guidelines from the American Academy of Allergy, Asthma & Immunology (AAAAI) provide detailed recommendations for diagnostic vaccination with pure pneumococcal polysaccharide vaccines (PPV). However, the degree of compliance with these guidelines and the utility of the guidelines in actual practice are undescribed. To address this, we systematically evaluated diagnostic vaccination in adult patients with suspected primary immunodeficiency diseases in a single tertiary center from 2011 to 2016 (n = 229). We found that full compliance with the AAAAI guidelines was achieved for only 39 patients (17%), suggesting that the guidelines are not easy to follow. Worse, interpretation according to the guidelines was heavily influenced by which serotype-specific antibodies that were used for the evaluation. We found that the arbitrary choices of serotype-specific antibodies could change the fraction of patients deemed to have ‘adequate immunity’ by a factor of four, exposing an inherent flaw in the guidelines. The flaw relates to dichotomous principles for data interpretation under the AAAAI guidelines. We therefore propose a revised protocol for diagnostic vaccination limited to PPV vaccination, subsequent antibody measurements, and data interpretation using Z-scores. The Z-score compiles multiple individual antibody levels, adjusted for different weighting, into one single continuous variable for each patient. In contrast to interpretation according to the AAAAI guidelines, the Z-scores were robust to variations in the choice of serotype-specific antibodies used for interpretation. Moreover, Z-scores revealed reduced immunity after vaccination in the patients with recurrent pneumonia (a typical symptom of antibody deficiency) compared with control patients. Assessment according to the AAAAI guidelines failed to detect this difference. We conclude that our simplified protocol and interpretation with Z-scores provides more robust clinical results and may enhance the value of diagnostic vaccination.
Corrigendum: Precise Monitoring of Pore Pressure at Boreholes Around Nankai Trough Toward Early Detecting Crustal Deformation

Precise Monitoring of Pore Pressure at Boreholes Around Nankai Trough Toward Early Detecting Crustal Deformation by Ariyoshi K. , Kimura T. , Miyazawa Y. , Varlamov S. , Iinuma T. , Nagano A. , Gomberg J., Araki E. , Miyama T. , Sueki K. , Yada S. , Hori T. , Takahashi N. and Kodaira S. (2021) Precise Monitoring of Pore Pressure at Boreholes Around Nankai Trough Toward Early Detecting Crustal Deformation. Front. Earth Sci. 9:717696. doi: 10.3389/feart.2021. 717696