Miracle-dz/UniFAR-FTUs huggingface dataset:
Unfavourable intrauterine environment contributes to abnormal gut microbiome and metabolome in twins

Objective Fetal growth restriction (FGR) is a devastating pregnancy complication that increases the risk of perinatal mortality and morbidity. This study aims to determine the combined and relative effects of genetic and intrauterine environments on neonatal microbial communities and to explore selective FGR-induced gut microbiota disruption, metabolic profile disturbances and possible outcomes. Design We profiled and compared the gut microbial colonisation of 150 pairs of twin neonates who were classified into four groups based on their chorionicity and discordance of fetal birth weight. Gut microbiota dysbiosis and faecal metabolic alterations were determined by 16S ribosomal RNA and metagenomic sequencing and metabolomics, and the long-term effects were explored by surveys of physical and neurocognitive development conducted after 2~3 years of follow-up. Results Adverse intrauterine environmental factors related to selective FGR dominate genetics in their effects of elevating bacterial diversity and altering the composition of early-life gut microbiota, and this effect is positively related to the severity of selective FGR in twins. The influence of genetic factors on gut microbes diminishes in the context of selective FGR. Gut microbiota dysbiosis in twin neonates with selective FGR and faecal metabolic alterations features decreased abundances of Enterococcus and Acinetobacter and downregulated methionine and cysteine levels. Correlation analysis indicates that the faecal cysteine level in early life is positively correlated with the physical and neurocognitive development of infants. Conclusion Dysbiotic microbiota profiles and pronounced metabolic alterations are associated with selective FGR affected by adverse intrauterine environments, emphasising the possible effects of dysbiosis on long-term neurobehavioural development.
Inter-arm blood pressure difference and cardiovascular risk estimation in primary care: a pilot study

Background Systolic inter-arm differences (IAD) in blood pressure (BP) contribute independently to cardiovascular risk estimates. This can be used to refine predicted risk and guide personalised interventions. Aim To model the effect of accounting for IAD in cardiovascular risk estimation in a primary care population free of pre-existing cardiovascular disease. Design & setting A cross-sectional analysis of people aged 40–75 years attending NHS Health Checks in one general practice in England. Method Simultaneous bilateral BP measurements were made during health checks. QRISK2, atherosclerotic cardiovascular disease (ASCVD), and Framingham cardiovascular risk scores were calculated before and after adjustment for IAD using previously published hazard ratios. Reclassification across guideline-recommended intervention thresholds was analysed. Results Data for 334 participants were analysed. Mean (standard deviation) QRISK2, ASCVD, and Framingham scores were 8.0 (6.9), 6.9 (6.5), and 10.7 (8.1), respectively, rising to 8.9 (7.7), 7.1 (6.7), and 11.2 (8.5) after adjustment for IAD. Thirteen (3.9%) participants were reclassified from below to above the 10% QRISK2 threshold, three (0.9%) for the ASCVD 10% threshold, and nine (2.7%) for the Framingham 15% threshold. Conclusion Knowledge of IAD can be used to refine cardiovascular risk estimates in primary care. By accounting for IAD, recommendations of interventions for primary prevention of cardiovascular disease can be personalised and treatment offered to those at greater than average risk. When assessing elevated clinic BP readings, both arms should be measured to allow fuller estimation of cardiovascular risk.
An assessment of agricultural extension services in irrigation schemes under RBDAs' control in Nigeria: The case of Kano River irrigation project

The National Irrigation Policy is based on boosting domestic agricultural production by using irrigation since rain fed production alone cannot meet demand. Achieving the goal of increasing agricultural production through harnessing of national irrigation potentials will depend on many factors; among which extension is likely to be one of the most important. For this purpose, this paper attempts to evaluate the extension delivery services for irrigated crop production within the Kano River Irrigation Project in Nigeria with the aim of proving their adequacy. Primary data were collected through the use of semi-structured questionnaires randomly administered to 80 farmers within the study area. Descriptive statistics were used to analyse it. The findings of the study indicate that the majority of the respondents find the extension services in the study area unavailable as neither the River Basin Development Authorities (RBDA), the Local Government Authorities (LGA), the Agricultural Development Projects (ADP) nor the Non-Governmental Organisations (NGOs) played significant extension delivery function in the area. Furthermore, most of the respondents do not belong to any farmer association or cooperative society. The Training and Visit system is the most preferred method of extension delivery in the study area and it is followed by the electronic media. However, the mobile phone is not considered a means of extension delivery by all of the respondents. The study concludes that the extension delivery system within the study area is grossly inadequate, and therefore, recommends the employment of more extension workers by the RBDA and the ADP; as well as encouraging and motivating the NGOs to reach out to the farmers.
Use of batch anion exchange technique for separation of κ-casein glycomacropeptide from bovine whey fraction

Abstract Bovine κ-casein glycomacropeptide (GMP) is a sialic acid containing glycopeptide, which is considered as a health promoting compound found in cheese whey. The study described in this research communication was undertaken to determine whether GMP with undetectable level of contaminating protein or phenylalanine can be isolated from bovine whey fraction using batch anion exchange technique with chitin as an adsorbent. A soluble whey fraction (SWF) prepared from 1 g whey protein isolate (WPI) was mixed with a slurry of 1 g chitin, and the mixture was incubated at pH 3.0. After incubation, the mixture was filtered, and the residue obtained (containing chitin-GMP complex) was washed with water and eluted stepwise with 0.5 M NaCl and 2.0 M NaCl. Most of GMP (corresponding to 75.8% of total sialic acid recovered) was eluted with 0.5 M NaCl. The recovered GMP accounted for 5.4% dry weight of WPI (or 18.9% dry weight of SWF). Amino acid analysis showed that there was no detectable level of contaminating amino acids including phenylalanine, histidine, arginine and tyrosine in the GMP fraction. It was concluded that the batch anion exchange method with chitin developed in this study can be used for the isolation of high purity GMP from bovine SWF.
Effectiveness of continuous femoral nerve block for pain relief after total knee arthroplasty: comparison with epidural patient-controlled analgesia and periarticular injection

Objective To compare the clinical outcomes among three analgesic techniques, continuous femoral nerve block (CFNB), epidural patient-controlled analgesia (EPCA) and periarticular injection (PAI), in patients undergoing total knee arthroplasty (TKA). Methods This retrospective case–control study enrolled patients that underwent TKA. Visual analogue scale (VAS) pain scores, sleep disturbance, additional opioid consumption and incidence of opioid-related side-effects were assessed. Results A total of 120 patients were categorized into three groups: EPCA (group A, n = 40), PAI (group B, n = 40) and CFNB (group C, n = 40). Group C had significantly lower VAS pain scores than groups A and B at 8, 12 and 24 h after TKA. There were no significant differences in VAS pain scores among the three groups from 48 h after TKA. Sleep quality on the first day after surgery was significantly better in group C than in groups A and B. Additional opioid consumption was significantly lower in the group C than in the groups A and B. Group C showed a lower rate of opioid-related side-effects than groups A and B. Conclusion CFNB was a more effective additional analgesic technique than EPCA or PAI for acute postoperative pain control within 24 h of TKA.
FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamide

Although full‐length fibroblast growth factor 7 (FGF7) blocks cyclophosphamide‐induced urothelial apoptosis in mice, limitations include high production costs because of its large size. We previously identified a small peptide derived from FGF2 that mitigated acute radiation syndrome as well as full‐length FGF2. Based on the sequence of the FGF2 peptide, we synthesized a corresponding 19 amino acid FGF7 peptide (FGF7p). Our objectives were to determine if systemic FGF7p triggered the downstream targets and protected against cyclophosphamide bladder injury similar to full‐length FGF7. We administered FGF7p or vehicle subcutaneously (SQ) to mice subjected to no injury or intraperitoneal (IP) cyclophosphamide and harvested bladders 1 day after injury. We then performed hematoxylin and eosin, TUNEL and immunofluorescence (IF) staining. In uninjured mice, a 20 mg/kg threshold FGF7p dose induced expression of phosphorylated (activated) FRS2α (pFRS2α), and pAKT in urothelium (consistent with cytoprotective effects of FGF7). We then gave FGF7p (20 mg/kg) or vehicle at 72 and 48 h prior to cyclophosphamide. One day after injury, TUNEL staining revealed many more apoptotic urothelial cells with vehicle treatment versus FGF7p treatment. IF for pAKT and readouts of two anti‐apoptotic AKT targets (BAD and mTORC1) revealed minimal staining with vehicle treatment, but strong urothelial expression for all markers with FGF7p treatment. In conclusion, FGF7p appears to block bladder urothelial apoptosis via AKT and its targets, similar to FGF7. FGF7p is much more inexpensive to make and has a longer shelf life and higher purity than FGF7.
Using weighted communication scoring procedures in naturalistic play samples: Preliminary validation in preschool‐aged boys with autism or fragile X syndrome

In the present study, we provide a preliminary evaluation of the validity and reliability of using weighting procedures to measure communication in play samples for preschool‐aged boys with autism or fragile X syndrome (FXS). Because weighting procedure communication scores (WPCSs) reflect growth in both communicative frequency and complexity, establishing the psychometrics of the component scores, in addition to the overall metric, affords investigators the opportunity to describe growth within and across skills. Results, for both groups, provide support regarding the psychometric appropriateness (i.e., convergent validity, divergent validity, and internal consistency) for all WPCSs. That said, a trend was observed for reliability scores to be slightly lower or more variable in boys with autism than in boys with FXS. Finally, although significant associations were observed in the associations between WPCSs across play contexts, contexts effects were observed for all three WPCSs. Together, results from this study provide promising preliminary data indicating the utility of using WPCSs in children with neurodevelopmental disabilities.
Solutions for Groundwater Flow to a Pumping Well with an Exponentially Decreasing Variable‐Rate in a Sloping Aquifer

During aquifer pumping tests in the field, the attenuation process of the pumping rate is generally monitored, and the aquifer may be slanted, especially in riverbank terraces, piedmont plain and other similar terrains. The combination of these two factors (attenuation process and aquifer slope) has not received enough academic attention, therefore, a two‐dimensional groundwater flow model is developed for an exponentially decreasing variable rate pumping well in a sloping aquifer in this study. The new semi‐analytical solution (based on a linearized free‐surface boundary) is obtained using the Laplace transform and finite Fourier cosine transform. Meanwhile, to depict the linearized boundary precisely with the first‐order free surface equation, a numerical model that considers the decline of the water table is also developed. Results show that under the effect of the variable rate, the time‐drawdown curve presents a downward trend at intermediate times. Additionally, the error caused by the linearization of the free‐surface equation on the analytical model is found to be acceptable except when the sloping angle is larger than π/6. Furthermore, since this study extends the work of Huang et al. (2014), who considered a constant pumping rate, the new solution was found better to interpret real pumping test data reported by Antonio and Pacheco (2002), and the laboratory experiment results. Overall, the new solution proves to be useful for parameter inversion accurately as the average pumping rate tended to underestimate hydraulic parameters when fitting short‐term pumping data.
Mesenchymal stromal cells promote the proliferation of basal stem cells and efficient epithelization in organotypic models of wound healing

Adipose derived mesenchymal stromal cells (ADSCs) represent a fascinating tool in the scenario of wound healing and regenerative medicine. Recent data already demonstrated that ADSCs could exert a stimulatory action on epithelial cells through secretion of soluble factors. The aim of the present study was to assess how ADSCs guide wound re‐epithelization in vitro in the presence of keratinocytes. We used an organotypic model of wound healing and we seeded keratinocytes on a ADSC‐induced dermal matrix. Conventional hematoxylin–eosin stain and immunohistochemistry staining for Ki67, p63 and pan‐keratins were performed at different timepoints. Histological sections of organotypic cultures showed complete coverage of the ADSC‐induced matrix by keratinocytes. Proliferation of basal stem cells was found to be the main mechanism responsible for epithelization of the dermis. In conclusion, ADSC do not only stimulate dermal regeneration through collagen deposition but also promote epithelization.
Impact of Palliative Care in End-of-Life of Fibrotic Interstitial Lung Disease Patients

Background: Interstitial lung disease (ILD) is associated with poor quality of life (QoL) and high symptom burden. Studies evaluating the benefits of palliative care examined mainly idiopathic pulmonary fibrosis (IPF) patients. We aim to examine the impact of palliative care on a broader group of fibrotic ILD patients. Methods: Single center retrospective cohort study comparing deceased ILD patients who received outpatient palliative care services (palliative-intervention group) against a usual care group. Results: Of 63 subjects, 26 (41%) were in the palliative-intervention group and 37 (59%) in the usual care group. Median time to palliative care referral was 8.6 (IQR .3–21.2) months. Dyspnea-related disability was greater in the palliative-intervention group [mMRC dyspnea score 3.5(IQR 2–4) vs 2(IQR 2–4), P = . 039], with more patients requiring long term oxygen therapy (70% vs 30%, P < .001). There was no difference in the median number of hospitalizations or length of stay in the last 6 months of life. Patients in the palliative-intervention group had a higher uptake of advance care planning (ACP) (39% vs 11%, P = .014), lower frequency of intensive care unit (ICU) admissions (5% vs 19%, P = .102) and were prescribed more opioids (96% vs 27%, P < .001) and benzodiazepines (39% vs 14%, P = .022). The palliative-intervention group experienced a longer median survival of 23.9 months (95% confidence interval [CI] 14.1–33.7) compared to the usual group (11.4 months [95% CI 5.4–17.3] (log-rank test: P = .023). Male gender was a strong predictor of 1-year mortality. Conclusions: The palliative-intervention group received earlier pharmacologic intervention for symptom relief. Healthcare utilization was not increased despite greater dyspnea-related disability.
Different Genes are Recruited During Convergent Evolution of Pregnancy and the Placenta

Abstract The repeated evolution of the same traits in distantly related groups (convergent evolution) raises a key question in evolutionary biology: do the same genes underpin convergent phenotypes? Here, we explore one such trait, viviparity (live birth), which, qualitative studies suggest, may indeed have evolved via genetic convergence. There are >150 independent origins of live birth in vertebrates, providing a uniquely powerful system to test the mechanisms underpinning convergence in morphology, physiology, and/or gene recruitment during pregnancy. We compared transcriptomic data from eight vertebrates (lizards, mammals, sharks) that gestate embryos within the uterus. Since many previous studies detected qualitative similarities in gene use during independent origins of pregnancy, we expected to find significant overlap in gene use in viviparous taxa. However, we found no more overlap in uterine gene expression associated with viviparity than we would expect by chance alone. Each viviparous lineage exhibits the same core set of uterine physiological functions. Yet, contrary to prevailing assumptions about this trait, we find that none of the same genes are differentially expressed in all viviparous lineages, or even in all viviparous amniote lineages. Therefore, across distantly related vertebrates, different genes have been recruited to support the morphological and physiological changes required for successful pregnancy. We conclude that redundancies in gene function have enabled the repeated evolution of viviparity through recruitment of different genes from genomic “toolboxes”, which are uniquely constrained by the ancestries of each lineage.
Antiparasitic treatment with itraconazole and amiodarone in 2 dogs with severe, symptomatic Chagas cardiomyopathy

Abstract Chagas cardiomyopathy, caused by the protozoal parasite Trypanosoma cruzi, is characterized by arrhythmias, myocardial damage, heart failure, and sudden death. We describe 2 dogs with severe, symptomatic Chagas cardiomyopathy characterized by myocardial dysfunction and electrocardiographic abnormalities that were managed with a combination of cardiac medications and antiparasitic treatment with itraconazole and amiodarone. Both dogs died suddenly within 6 months of diagnosis. These cases highlight the need for early detection of Chagas disease in dogs and continued research to develop effective antiparasitic treatment protocols.
The COVID-19 Humoral Immunological Status Induced by CoronaVac and AstraZeneca Vaccines Significantly Benefits from a Booster Shot with the Pfizer Vaccine

COVID-19 continues to spread around the world despite significant progress in vaccine distribution and population immunity. The dynamics of the antiviral antibody response postvaccination is critical to evaluate vaccine effectiveness across different vaccine platforms and over time. ABSTRACT A third vaccine dose against COVID-19 is already a reality in some countries around the world. In this study, we aimed to evaluate the effectiveness of the Brazilian immunization policy for COVID-19, which involves a booster shot. Participants (n = 210) provided serum samples, which were subjected to enzyme-linked immunosorbent assay (ELISA). Immunological profiles were defined as individuals with or without previous SARS-CoV-2 infection who received at least one vaccine dose in the immunization regimens of AstraZeneca, CoronaVac, or CoronaVac plus a booster shot with Pfizer. In addition, nonvaccinated/infected individuals were also included. As main results, we observed that the numbers of infected individuals were significantly reduced among those who were vaccinated, even with one dose. This result indicates that vaccines are highly protective against COVID-19. However, we observed a significant tendency of serum level decreases of specific antibodies over the time after the second dose. In contrast, the booster shot with the Pfizer vaccine after a CoronaVac immunization regimen showed a significant increase in the specific SARS-CoV-2 IgG serum levels. Moreover, we found that vaccination induced a significantly higher humoral immunological status than only the natural infection with SARS-CoV-2. Collectively, results presented here indicate that vaccines are necessary to induce a robust immunological status, which is maintained, restored, or even improved by booster shots. IMPORTANCE COVID-19 continues to spread around the world despite significant progress in vaccine distribution and population immunity. The dynamics of the antiviral antibody response postvaccination is critical to evaluate vaccine effectiveness across different vaccine platforms and over time. In this study, we evaluate the serum levels of antiviral antibodies in patients from Brazil that received either the CoronaVac or the AstraZeneca vaccine. We found that antibody levels wane over time, vaccines induce protective immunity, and humoral immunity is enhanced with a third vaccine dose. This study reveals that the COVID-19 humoral immunological status induced by vaccines significantly benefits from a booster shot.
Epidermal growth factor receptor-targeted therapy for the treatment of non-small cell lung cancer: a review of phase II and III trials

ABSTRACT Introduction Epidermal growth factor receptor (EGFR) is one of the most common driver gene mutations in non-small-cell lung cancer (NSCLC). EGFR-tyrosine kinase inhibitors (TKIs) monotherapy and EGFR-TKI combined with chemotherapy or anti-angiogenesis drugs have significantly prolonged the survival of patients with EGFR-mutant NSCLC. However, disease progression caused by acquired resistance to EGFR-TKIs is inevitable. And patients with EGFR exon 20ins showed limited efficacy to EGFR-TKIs. Areas covered In this review, we initially evaluated the efficacy of existing treatments for EGFR-mutant NSCLC. Second, we reviewed the ongoing phase II and III clinical trials, provided the latest results, discussed the scientific rationale of these trials and the potential development issues. Expert opinion The application of EGFR-TKIs has greatly changed the therapeutic strategies for advanced and resected NSCLC with EGFR mutations, and the 5-year overall survival (OS) rate for advanced NSCLC was close to 40%. The current research direction for the treatment of patients with EGFR mutations focuses on the following three aspects: uncommon EGFR mutation subtypes, brain metastases, and EGFR TKI-based combination therapy. Future studies on EGFR-mutant NSCLC therapy will focus on overcoming EGFR-TKI-related resistance, preventing drug resistance in advance, and developing bispecific antibody drugs.