This paper presents a case with type 2 diabetes mellitus on a very low-carbohydrate diet who developed euglycemic diabetic ketoacidosis (EDKA) 3 days after starting sodium-glucose cotransporter 2 inhibitors (SGLT2i). When initiating SGLT2i, healthcare providers should confirm the implementation of a low-carbohydrate diet and provide intensive guidance to prevent EDKA.

A quantitative structural analysis was carried out to predict the physical properties of boric acid structure. A topological descriptor of chemical molecule structure is a numerical value that distinguishes between a base structure and its branching pattern in the knowledge of chemical, physical, and biological aspects of molecular structure. In modern chemistry, theoretical chemistry, pharmacology, toxicology, and environmental chemistry, a large number of numerical graph invariants (topological indices) have been established and used for correlation analysis. In this paper, edge-version of distance based topological descriptors like edge Wiener, edge Szeged, edge PI and vertex-edge Wiener are computed for the structure of boric acid graphite sheet and Theta, Omega, Sd and PI polynomials and their subsequent topological indices for boric acid graphite structure are quantified. Further, using Theta and Omega polynomials, we devise a new approach for calculating the PI and Sd indices.

In order to obtain the dominant immunogen of the protein encoded by p113/p126 family members of Mycoplasma ovipneumoniae. In this study, p113/p126 family recombinant proteins were prepared. We evaluated the antibody level induced by the recombinant protein of each member in the family and its binding ability with the whole bacterial protein. The binding ability of recombinant protein to whole bacterial protein was also evaluated. p113/p126 family members were rich in antigen epitopes. The recombinant proteins (rP128, rP126, and rP113) have the strongest binding ability to the serum of infected animals and belonged to the dominant immunogen. Mice immunized with recombinant protein could produce specific antibodies. The antibody produced by immunizing mice with recombinant proteins (rP113, rP109, and rP130) can effectively bind to bacterial protein. In summary, these results provided a basis for further research on the development of subunit vaccine and the establishment of serological diagnosis methods.

A document by Alexander Keller. Click on the document to view its contents.

Aims: Posaconazole is often used for the prophylaxis and treatment of invasive fungal infections (IFI). However, intra- and inter-individual differences and drug interactions affect the efficacy and safety of posaconazole. Precision dosing of posaconazole based on the population pharmacokinetic (PopPK) model may assist in making significant clinical decisions. This review aimed to comprehensively summarize the published PopPK models of posaconazole and analyze covariates that significantly influence posaconazole exposure. Methods: Articles published until May 2022 for PopPK analysis of posaconazole were searched in PubMed and EMBASE databases. Demographic characteristics, model characteristics, and results of PopPK analysis were extracted from the selected articles. In addition, the steady-state pharmacokinetic profiles of posaconazole were simulated at different covariate levels and dosing regimens. Results： Out of the 13 studies included in our review, nine studies included adults, three included children, and one included both adults and children. All oral administration models were one-compartment models, and all intravenous administration models were two-compartment models. Body weight, proton pump inhibitors, and incidence of diarrhea were found to be important covariates. In addition, age, sex, total protein, rifampin, phenytoin, intake of nutritional supplements, levels of bilirubin and gamma-glutamyl transferase, and administration of chemotherapy also appeared as covariates in several PopPK models. Conclusion: Posaconazole exposure was found to be influenced by various factors such as the type of formulation, the incidence of diarrhea, body weight, and use of concomitant medications. It was concluded that routine therapeutic drug monitoring was required for dose adjustment and in promoting individualized dosing.

Title: BRAFMutation in Neuroblastoma: A Rare FindingAuthors: Sara C Hutchins1, Sara R Ferguson1, Geling Li2, Elizabeth A Beierle3*, Elizabeth Alva1

Planted vegetation is considered one of the most important soil-forming factors in the reclamation of degraded post-mining lands for forestry. The objective of this study was to compare the effect of N-fixing tree species and non-N-fixing species on the organic phosphorus (P org) forms in technosols developing from various substrates. Samples were taken from the uppermost layer (depth 0 – 5 cm) of technosols afforested with black locust ( Robinia pseudoaccaccia), black alder ( Alnus glutinosa), silver birch ( Betula pendula) and Scots pine ( Pinus sylvestris). Samples of the tree foliage and the O horizons were taken as well. The studied technosols developed from Quaternary sands (Sands), fly ashes after lignite combustion (Ashes) and Miocene clays (Clays). The soil samples were measured for the contents of labile (P Olab) and moderately labile organic phosphorus (P Omod), phosphorus contained in fulvic and humic acids (P fulv and P hum, respectively) and residual organic phosphorus (P Ores). The foliage and O horizon samples were measured for the concentrations of C, N and P. The N-fixing trees had higher P concentration in the foliage than non-N-fixing species. However, in the O horizon the highest P concentration was determined under birch and not under N-fixers. The effect of tree species on the organic P (P org) concentrations in the mineral soil was limited with significantly lower P org concentrations under pine. Soil under this species contained less P fulv, P hum and P Ores. However, the percentages of P Olab, P Omod, P fulv, P hum and P Ores in soil P org were nearly the same under all tree species. The largest effect on the P org concentration and on the contents of particular P org fractions was from the substrate type. Sands contained much less P org than the Clays and Ashes but their percentage of P Olab in P org was much higher than in two other substrates. We conclude that N-fixing trees do not affect the concentration of labile organic P and the major factor controlling this P org fraction is the soil substrate quality.

We presented a patient with an advanced stage of endomyocardial fibrosis (EMF) who immigrated from Brazil to Framingham, Massachusetts. EMF is an extremely rare etiology of heart failure in Europe and North America, although the prevalence is high in tropical countries, including Brazil. However, as presented in our case, the incidence of EMF would increase with sporadic cases from immigration to temperate countries. Our case would help raise awareness and familiarity in diagnosing EMF, a rare and perhaps one of the most underappreciated causes of heart failure.

UV-B regulates the metabolism of many important substances, such as hormones, ascorbic acid (AsA) and secondary metabolites. However, the mechanism by which UV-B regulates AsA metabolism, especially signal transduction, is largely unclear. Here, we report that UV-B promotes the accumulation of AsA and the production of ethylene in cucumber seedlings. However, when the ethylene signal is blocked, UV-B no longer promotes the accumulation of AsA in cucumber leaves. This indicates that the ethylene signal is a key factor enabling UV-B to regulate AsA levels. The q-PCR results show that UV-B induces the expression of the CsACO and CsACS genes, which, in turn, promotes the biosynthesis of ethylene; thus, ethylene production is promoted and the ethylene signal is activated. Moreover, the expression of the ethylene response factor CsERF39 is up-regulated through a series of UV-B signal transduction. Knockout of CsERF39 and CsGLDH results in a reduced AsA pool in cucumber leaves. Furthermore, we identified CsGLDH as a direct target for CsERF39 to regulate AsA biosynthesis, by q-PCR analysis, molecular experiments and genetic data. Therefore, CsACS, CsACO, CsERF39 and CsGLDH are involved in the regulation of AsA biosynthesis by UV-B through the ethylene signal transcription cascade.

To improve the taxonomy and systematics of Porcellanidae within the evolution of Anomura, we describe the complete mitochondrial genomes (mitogenomes) sequence of Pisidia serratifrons, which is 15,344 bp in size, contains the entire set of 37 genes, and has an AT-rich region. The genome composition showed a high AT content of the mitogenomes was 74.29%, and exhibited a positive AT-skew (0.017) and a negative GC-skew (-0.246). Compared with the pan-crustacean ground pattern, at least five gene clusters (or genes) are significantly different with the typical genes, involving eleven tRNA genes and four PCGs, and the tandem duplication/random loss and recombination models were used to explain the observed large-scale gene rearrangements. The phylogenetic results showed that all Porcellanidae species clustered together as a group with well supported. Most Anomura superfamilies were found to be monophyletic, except Paguroidea. In general, the results obtained in this study will contribute to a better understanding of gene rearrangements in Porcellanidae mitogenomes and provide new insights into the phylogeny of Anomura.

Desert areas occupy approximately 25% of total land area and are characterized by scarce precipitation, poor soil conditions, and a harsh ecological environment. Desertification may result in the loss of unique biological resources. Therefore, exploring the biodiversity of deserts and the causal factors of desertification is necessary to develop future solutions to global desertification. The desert area in northwest China is an important part of the arid zone of central Asia as it was traveled during the ancient Silk Road and witnessed the rise and fall of many civilizations, making it an ideal location for desertification research. This study utilized environmental DNA in the surface soil along the eastern part of the Silk Road and DNA metabarcoding technology. Bioinformatic analysis identified 782 plant species belonging to 505 genera and 133 families, and plant species diversity gradually decreased from east to west along the Silk Road. Temperature, altitude, and longitude were the main factors affecting plant species diversity in the area, while the impact of precipitation was relatively small. Correlation analysis between species diversity, population density, and major human settlements revealed that human activity significantly affected plant species diversity. Our study successfully used environmental DNA and metabarcoding technology to reveal the plant species diversity and its influencing factors for a large-scale desert area, which will provide a fundamental and theoretical basis for desert management and biodiversity protection.

TITLE PAGETITLE OF THE MANUSCRIPT : SUCCESSFUL PREGNANCY AND CANCER OUTCOMES WITH IPILIMUMAB AND NIVOLUMAB FOR METASTATIC RENAL CELL CARCINOMARUNNING HEAD : Ipilimumab and nivolumab during pregnancy in renal cell carcinomaAUTHOR LIST : Francisco Zambrana1,3, Carmen Barbancho1,4, Miriam Huelves1,5, Yolanda Martín1,3, Marta Muñoz de Lengaria1,6, Guillermo de Velasco2AUTHOR´S INSTITUTION :1 Infanta Sofía University Hospital. Paseo de Europa 34. Madrid 28702. SPAIN.2 Doce de Octubre University Hospital. Avda. de Córdoba s/n. Madrid 28041. SPAIN3 Department of Medical Oncology.4 Department of Gynaecology and Obstetrics.5 Department of Radiology.6 Department of PathologyCORRESPONDING AUTHOR´S CONTACT INFORMATION :Francisco Zambrana, M.D. Hospital Universitario Infanta Sofía. Department of Medical Oncology. Paseo de Europa 34. Madrid 28702. SPAIN Phone number: +34 661222026 e-mail:currozambrana@gmail.comTwitter handle: @curroncoNothing to disclose.No funding sources.All authors have reviewed and accepted the manuscript.We have obtained written informed consent to publish the report from the patient.Word Count : 1256Unstructured Abstract : 122 wordsTables/Figures : noneReferences : 10SUCCESSFUL PREGNANCY AND CANCER OUTCOMES WITH IPILIMUMAB AND NIVOLUMAB FOR METASTATIC RENAL CELL CARCINOMA

Objectives: Universal implementation of cystic fibrosis (CF) newborn screening (NBS) has led to the diagnostic dilemma of infants with CF screen positive, inconclusive diagnosis (CFSPID), for which there is limited guidance regarding prognosis and standardized care. Rates of reclassification from CFSPID to CF vary and risk factors for reclassification are unknown. We investigated whether clinical characteristics are associated with risk of reclassification from CFSPID to a CF diagnosis. Methods: Children with a positive CF NBS were recruited from two sites in California. Retrospective, longitudinal, and cross-sectional data were collected. A subset of subjects had nasal epithelial cells collected for CFTR functional assessment. Multivariate logistic regression was used to assess the risk of CFSPID-to-CF reclassification. Results: A total of 112 children completed the study (CF=53, CFSPID=59). Phenotypic characteristics between groups showed differences in pancreatic insufficiency prevalence, immunoreactive trypsinogen (IRT) levels, and Pseudomonas aeruginosa (PSA) colonization. Spirometry measures were not different between groups. Nasal epithelial cells from 10 subjects showed 7-30% of wild type (WT)-CFTR function in those who reclassified and 27-67% of WT-CFTR function in those who retained the CFSPID designation. Modeling revealed that increasing sweat chloride concentration (sw[Cl -]) and PSA colonization were independent risk factors for reclassification to CF. Conclusion: Increasing sw[Cl -] and history of PSA colonization are associated with risk of reclassification from CFSPID to CF in a population with high IRT and two CFTR variants. Close follow-up to monitor phenotypic changes remains critical in this population. The role of CFTR functional assays in this population requires further exploration.

Stream channel incision and deposition are common after wildfire, and these geomorphic changes may impact runoff mechanisms and the composition of pre-event and event water in runoff. To investigate this, we monitored discharge and electrical conductivity at 6 nested sites within a 15.5 km 2 watershed in the northern Colorado Front Range that had recently burned, experienced large flooding, and well-documented and significant channel erosion and deposition. Over the study period, the watershed experienced seven precipitation events. For each hydrograph, we separate baseflow from runoff using a new method to characterize and account for the strong diurnal signal in the baseflow. Electrical conductivity is used as a tracer in a two-component end-member mixing analysis to separate the event hydrographs into event and pre-event water. Correlation coefficients were computed between key variables of the hydrologic response (such as runoff ratio, volumes of event and pre-event water) to storm and basin characteristics (including stream channel erosion/deposition, fraction of high/moderate burn severity, precipitation intensity, and antecedent precipitation). The strength and significance of correlations was found to vary seasonally. In the early season, event and pre-event volumes did not vary significantly with basin or storm characteristics. In the late season, antecedent precipitation correlated with a decrease in event runoff (R 2 = 0.34) and total runoff (R 2 = 0.40), increased precipitation intensity correlated with an increase in event runoff (R 2 = 0.48), and local erosion correlated with an increase in pre-event runoff (R 2 = 0.60) and total runoff (R 2 = 0.53). These findings indicate that seasonality and post-fire stream channel erosion influence the makeup of runoff response, most likely through their impact on the gradient of the near-stream groundwater table.

A slot loaded rectangular antenna is designed to resonate at two distinct frequencies. Initially, the antenna is designed using high frequency simulation software CST microwave Studio. The antenna is designed by introducing one slot near center and other slots on both side of the central slot, placed diagonally, to observe frequency variation leading to tuning the designed frequency. Addition of slots on the patch with variations in feed point location shows dual frequency tuning behavior at two resonant frequencies. Variations of the slot distance with respect to each other along with changing the feed point location is studied with tuning of the resonant frequency within the same band (L and S -Band). Both simulated and measured results indicate that RL values are not degraded thus performance of the antenna is not disturbed with dual frequency behavior of the antenna with tuning of the frequency/ frequencies.

Sustainable water management in semi-arid agriculture practices requires quantitative knowledge of water fluxes within the soil-vegetation-atmosphere system. Therefore, we used stable-isotope approaches to evaluate evaporation (Ea), transpiration (Ta), and groundwater recharge (R) at sites in Senegal's Groundnut basin and Ferlo Valley pasture region during the pre-monsoon, monsoon, and post-monsoon seasons of 2021. The approaches were based upon (i) the isothermal evaporation model (for quantifying Ea); (ii) water and isotope mass balances (to partition Ea and Ta for groundnut and pasture); and (iii) the piston displacement method (for estimating R). Ea losses derived from the isothermal evaporation model corresponded primarily to Stage II evaporation, and ranged from 0.02–0.09 mm d-1 in the Groundnut basin, versus 0.02–0.11 mm d-1 in Ferlo. At the groundnut site, Ea rates ranged from 0.01 to 0.69 mm d-1; Ta was in the range 0.55–2.29 mm d-1; and the Ta/ETa ratio was 74–90%. At the pasture site, the ranges were 0.02–0.39 mm d-1 for Ea; 0.9–1.69 mm d-1 for Ta; and 62–90 % for Ta/ETa.  The ETa value derived for the groundnut site via the isotope approach was similar to those from eddy covariance measurements, and also to the results from a previous validated HYDRUS-1D model. However, the HYDRUS-1D model gave a lower Ta/ETa ratio (23.2%). The computed groundwater recharge for the groundnut site amounted to less than 2% of the local annual precipitation. Recommendations are made regarding protocols for preventing changes to isotopic compositions of water in samples that are collected in remote arid regions, but must be analysed days later. The article ends with suggestions for studies to follow up on evidence that local aquifers are being recharged via preferential pathways

A S wave function's expansion for 2 electron atoms and ions is obtained and the leading coefficients are reported.

In this letter, a low-voltage passive first-order noise shaping charge-redistribution successive approximation register (SAR) ADC with energy-efficient switching method is proposed. The energy-efficient switching method is achieved by one-side switching instead (OSSI) method and higher-bit switching instead (HBSI) method. The architecture is modified to realize the noise-shaping loop properly. We present a passive integrator with a dynamic DC offset to address the path gain error from the varying voltage on the capacitor array at each quantization step. Simulation results on a 180nm CMOS technology operated at 0.6V supply and 25kHz sampling rate show 130nW power consumption with a peak SNDR of 70.3dB.

The fermentation method for preparing SA is distinguished by low energy consumption and environmental friendliness, but the resulting products mainly exist in form of disodium succinate (DSA). Direct esterification of DSA using CO2 and CH3OH as esterification reagent to produce dimethyl succinate (DMS) can avoid use of inorganic acids in downstream esterification industry of bio-based DSA. On basis of high-resolution mass spectrometry analysis and quantum theoretical calculation, the process of DSA direct esterification involved sequentially forming 3-carboxypropanoate, monomethyl succinate (MMS), and DMS. Furthermore, the reaction kinetics of DSA direct esterification was investigated by experiment and numerical simulation method, where the reaction kinetics equation and reaction rate constant were obtained. The activation energy for the generated process of MMS by DSA was 37.15 kJ/mol, while the one for the formed process of DMS from MMS was 85.80 kJ/mol, indicating the latter was the speed control step of DSA direct esterification.

Title: Reel syndrome, Lead Macrodislodgement.Shubash Adhikari MD FACP2, Frank Annie PhD1, Muhammad Amer MD FACP FACC FHRS21CAMC Health Education and Research Institute3200 MacCorkle Ave. SE, Charleston, WV 25304.2CAMC Cardiology3200 MacCorkle Ave. SE, Charleston, WV, 25304

Background and Purpose Polypharmacotherapy is a growing phenomenon associated with adverse effects in older adults. We assessed the potential confounding effects of cumulative anticholinergic burden (ACB) in patients who were hospitalised with falls. Methods A non-interventional, prospective cohort study of unselected, acute admissions aged ≥65 years. Data were derived from electronic patient health records. Results were analysed to determine the frequency of polypharmacotherapy and degree of ACB and their relationship to falls risk. Primary outcomes were polypharmacotherapy, defined by ≥5 medications, and ACB score. Key Results 411 consecutive subjects were included, mean age 83·8 ± 8·0 years: 40·6% male. 38·4% were admitted with fall. Incidence of polypharmacotherapy was 80·8%, (88·0% and 76·3% among those admitted with and without fall respectively). Incidence of ACB score of 0, 1, 2, ≥3 was 38·7%, 20·9%, 14·6% and 25·8% respectively. On multivariate analysis, age (OR=1·03, [1·0 ; 1·05], p= 0·0494), ACB score (OR=1.15, [1.02 ; 1.29], p= 0.0245), polypharmacotherapy (OR=2·14, [1·19 ; 3·87], p= 0·0115) but not Charlson Comorbidity Index (OR=0·92, [0·81 ; 1·04], p= 0·1723) were significantly associated with higher falls rate. Of patients admitted with fall, 29·8% had drug-related orthostatic hypotension, 24·7% had drug-related bradycardia, 37·3% were prescribed centrally acting drugs and 12·0% were taking inappropriate hypoglycaemic agents. Interpretation Polypharmacotherapy results in cumulative ACB and both are significantly associated with falls risk in older adults. The presence of polypharmacotherapy and each unit rise in ACB score have a stronger effect of increasing falls risk compared to age and comorbidities.

We report the case of a teenager with a neurofibromatosis Type 2 (NF2) presenting a locked-in syndrome due to a brainstem ischemic syndrome. The presence of sudden or rapidly worsening onset of neurological deficits in NF2 patients, should evoke this underknown entity and not only tumors as predisposed by NF2.

It is widely admitted that the use of renewable energy is experiencing significant growth throughout the entire world. With the increasing demand for electric power, mainly for the needs of remote, desert and mountainous regions, the photovoltaic energy systems started finding great applications, particularly in telecommunication and water pumping systems.

Objectives— Early screening and dynamic monitoring of pulmonary vascular disease (PVD) in bronchopulmonary dysplasia (BPD) high-risk infants is of great clinical significance. Pulmonary artery acceleration time (PAAT) is a reliable and non-invasive method for assessing PVD in children over 1 year, but to date, few studies have used PAAT to assess pulmonary hemodynamics of preterm infants, especially those with BPD. Through dynamic monitoring the main hemodynamic indicators reflected PVD after birth, this study aimed to assess the value of PAAT in evaluating early PVD in BPD infants. Methods— 81 preterm infants at risk of BPD were divided into BPD and non-BPD groups according to whether BPD occurred. Clinical characteristics, PAAT, right ventricular ejection time (RVET) and other main hemodynamic indicators at 4 different time points after birth were studied and compared. Results— PAAT and PAAT/RVET increased gradually within 72 hours after birth in the BPD group ( P < 0.05), but the curve tended to be flat over time after 72 hours( P > 0.05). At PMA32 and 36 weeks, the PAAT (49.7±4.8 vs.54.8±5.7, P=0.001; 50.0±5.3 vs.57.0±5.3, P=0.001) and PAAT/RVET (0.33 ± 0.04 vs. 0.35 ± 0.03, P=0.001; 0.34 ± 0.03 vs. 0.37 ± 0.04, P = 0.001) in BPD group were significantly lower than those in the non-BPD group. Conclusions— PAAT and PAAT/RVET in the BPD group infants showed different change patterns compared to non-BPD group infants. PAAT can be used as a noninvasive and reliable screening method for screening and dynamic monitoring of PVD in BPD high-risk infants.