Landscapes of gut bacterial and fecal metabolic signatures and their relationship in severe preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific disease leading to maternal and perinatal morbidity. Hypertension and inflammation are the main characteristics of preeclampsia. Many factors can lead to hypertension and inflammation, including gut microbiota which plays an important role in hypertension and inflammation in humans. However, alterations to the gut microbiome and fecal metabolome, and their relationships in severe preeclampsia are not well known. This study aims to identify biomarkers significantly associated with severe preeclampsia and provide a knowledge base for treatments regulating the gut microbiome. METHODS: In this study, fecal samples were collected from individuals with severe preeclampsia and healthy controls for shotgun metagenomic sequencing to evaluate changes in gut microbiota composition. Quantitative polymerase chain reaction analysis was used to validate the reliability of our shotgun metagenomic sequencing results. Additionally, untargeted metabolomics analysis was performed to measure fecal metabolome concentrations. RESULTS: We identified several Lactobacillaceae that were significantly enriched in the gut of healthy controls, including Limosilactobacillus fermentum, the key biomarker distinguishing severe preeclampsia from healthy controls. Limosilactobacillus fermentum was significantly associated with shifts in KEGG Orthology (KO) genes and KEGG pathways of the gut microbiome in severe preeclampsia, such as flagellar assembly. Untargeted fecal metabolome analysis found that severe preeclampsia had higher concentrations of Phenylpropanoate and Agmatine. Increased concentrations of Phenylpropanoate and Agmatine were associated with the abundance of Limosilactobacillus fermentum. Furthermore, all metabolites with higher abundances in healthy controls were enriched in the arginine and proline metabolism pathway. CONCLUSION: Our research indicates that changes in metabolites, possibly due to the gut microbe Limosilactobacillus fermentum, can contribute to the development of severe preeclampsia. This study provides insights into the interaction between gut microbiome and fecal metabolites and offers a basis for improving severe preeclampsia by modulating the gut microbiome.

Enhanced nonlinear effects in femtosecond laser-inscribed depressed cladding waveguides in sapphire crystals.

High-performance depressed cladding waveguides can be fabricated in crystals using ultrafast laser inscription. The investigation of nonlinear phenomena, which manifest during the transmission of high peak power femtosecond pulses within waveguides, holds significant importance for their practical integration into waveguide lasers and waveguide-based components, among other pioneering applications. In this study, the depressed cladding waveguides were successfully prepared in sapphire crystal by a femtosecond laser. The nonlinear phenomena occurring in this waveguide were investigated. The experimental results show that the nonlinearity in the depressed cladding waveguides is significantly enhanced compared with that of the bulk. This enhancement notably manifests through augmented nonlinear losses (NLs) and the third harmonic (TH) blueshift increase. Meanwhile, we theoretically investigate the influence of nonlinear effects on the TH, such as self-phase modulation (SPM), cross-phase modulation (XPM), and group delay. Our results reveal that the phase mismatch between the TH and the pump pulses is the main reason for the asymmetric broadening and blueshift of the TH spectrum. Our study reveals the unique nonlinear properties of the waveguides and lays the foundation for further relevant studies and applications of such waveguides.

Ring Contraction by Rearrangement of Sterically Congested Cyclic (Amino)(aryl)carbenes.

The rearrangement of sterically congested cyclic (amino)(aryl)carbenes (CAArCs) by the reaction of related iminium salts with potassium bis(trimethylsilyl)amide is reported, allowing for forming benzocyclobutanimines via a ring contraction process. Mechanistic studies by theoretical calculations indicate that the formation of conjugated ketenimines as intermediates could be considered, in which steric hindrance caused by N-alkyl motifs of CAArCs plays an important role in promoting the ring-opening by the cleavage of C-N bond.

Factors Associated with Reliance on Audio-Only Technology (Telephone) for Completion of Telepsychiatry Visits.

Introduction: The ability to access telepsychiatry through audio-video technology versus audio-only (telephone) technology potentially leads to inequitable outcomes. This study examines the characteristics of patients who relied on the telephone to complete outpatient telepsychiatry visits in a large health system. Methods: This is a retrospective analysis of all telepsychiatry outpatient visits conducted from May 1, 2020, to December 31, 2021. Demographic, clinical, and socioeconomic factors were extracted from the electronic health record. Two-sample t tests were used for continuous variables and χ2 tests for categorical variables for bivariate analyses. Multiple logistic regression was used to examine the association between only telephone visits and all input variables. Results: Eight hundred ninety-four (8.9%) patients completed all visits only by telephone during the study period. In bivariate analyses, factors associated with telephone-only visits included male sex, non-English primary language, Black race, unmarried status, non-Hispanic ethnicity, older age, Medicare enrollment, uninsured status, and higher social vulnerability index (SVI). Psychiatric diagnoses associated with only telephone visits included substance use disorders and psychotic disorders. In multivariate analyses, factors associated with higher odds of only telephone visits included older age, inactive patient portal, comorbid diabetes, higher SVI, and higher broadband adoption. Psychiatric diagnoses associated with higher odds of completing only telephone visits included psychotic disorders, substance use disorders, or intellectual/developmental disabilities. Conclusions: Several patient-level factors are associated with a reliance on the telephone to complete telepsychiatry appointments.

Reductive transamidation of tertiary amides with nitroarenes enabled by magnesium and chlorosilane.

Reported here is the reductive transamidation of tertiary amides with nitroarenes promoted by main group metal magnesium and chlorosilane. The reaction uses commercially available and air-stable nitroarenes as nitrogen sources, so it can occur under transition-metal- and ligand-free conditions, thus providing a step-economic and cost-effective strategy for forming centrally important secondary amides. Several biologically interesting amide motifs are readily accessible by the Mg-promoted reductive transamidation.

Influence of optical surface distortion in a cylindrical Offner stretcher on the far-field signal-to-noise ratio.

In a stretcher, the surface distortion of the optical elements can introduce spectral phase modulations into the laser, which can affect the laser's signal-to-noise ratio. In this paper, by combining ray tracing methods and angular spectrum diffraction methods, the impact of the mid-frequency surface distortion of the optical elements in an cylindrical Offner stretcher on the far-field signal-to-noise ratio of the laser is simulated. The results show that reducing the spatial chirp on the convex cylindrical mirror can effectively improve the far-field signal-to-noise ratio of the laser, and two methods to improve the far-field signal-to-noise ratio are presented.

DIA-based proteomics analysis of serum-derived exosomal proteins as potential candidate biomarkers for intrahepatic cholestasis in pregnancy.

BACKGROUND: Data-independent acquisition (DIA) is one of the most powerful and reproducible proteomic technologies for large-scale digital qualitative and quantitative research. The aim of this study was to use proteomic methodologies for the identification of biomarkers that are over or underexpressed in women with intrahepatic cholestasis of pregnancy (ICP) compared with controls and discover a potential biomarker panel for ICP detection. METHODS: The participants included 11 ICP patients and 11 healthy pregnant women as controls. The clinical characteristic data and the laboratory biochemical data were collected at the time of recruitment. Then, a data-independent acquisition (DIA)-based proteomics approach was used to identify differentially expressed proteins (DEPs) in serum exosomes between ICP patients and controls. Finally, bioinformatics analysis was used to identify the relevant processes in which these DEPs were involved. RESULTS: The proteomics results showed that there were 162 DEPs in serum exosomes between pregnant women with ICP and healthy pregnant women, of which 106 were upregulated and 56 were downregulated in ICP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the identified proteins were functionally related to specific cell processes including apoptosis, lipid metabolism, immune response and cell proliferation, and metabolic disorders, suggesting that these may be primary causative factors in ICP pathogenesis. Meanwhile, complement and coagulation cascades may be closely related to the development of ICP. Receiver operating characteristic curve (ROC) analysis showed that the area under the curve values of Elongation factor 1-alpha 1, Beta-2-glycoprotein I, Zinc finger protein 238, CP protein and Ficolin-3 were all approximately 0.9, indicating the promising diagnostic value of these proteins. CONCLUSIONS: This preliminary work provides a better understanding of the proteomic alterations in the serum exosomes of pregnant women with ICP.

A Comprehensive Examination of Pediatric Behavioral Health Service Demand and Utilization in a Large, Academic Health System from 2019 to 2021.

Studies of the effects of COVID-19 on youth suggest a worsening in mental health globally. We performed a retrospective analysis of data from January 2019-November 2021 for all outpatient referrals, as well as outpatient, inpatient, and emergency department (ED) encounters for behavioral health (BH) reasons in children aged < 18 in a large academic health system in the United States. Mean weekly rates of outpatient psychiatry referrals, outpatient psychiatry visits, ED visits, and inpatient admissions for BH reasons were compared between pre-pandemic and pandemic periods. The average weekly rate of ambulatory referrals (8.0 ± 0.33 to 9.4 ± 0.31) and completed appointments (194.2 ± 0.72 to 213.1 ± 0.71) significantly increased during the pandemic, driven largely by teenagers. The weekly average of ED pediatric encounters for BH did not increase during the pandemic, although the percentage of all pediatric ED encounters that were for BH did increase from 2.6 to 4.1% (p < 0.001). Length of stay for pediatric BH ED patients increased from 1.59 ± 0.09 days pre-pandemic to 1.91 ± 0.11 days post-pandemic (p < 0.0001). Inpatient admissions for BH reasons overall decreased during the pandemic, due to a decrease in inpatient psychiatric bed capacity. However, the weekly percentage of inpatient hospitalizations for BH reasons that occurred on medical units increased during the pandemic (15.2% ± 2.8-24.6% ± 4.1% (p = 0.0006)). Taken together, our data suggest the COVID-19 pandemic had varying degrees of impact, depending on the setting of care.

Chemoselective Three-Component Geminal Cross Couplings of Dihaloalkanes with Cr Catalysis: Rapid Access to Tertiary and Quaternary Alkanes via a Metal-Carbene Intermediate.

Geminal cross couplings using multiple components enable the formation of several different bonds at one site in the building of tertiary and quaternary alkanes. Nevertheless, there are remaining issues of concern-cleavage of two geminal bonds and control of selectivity present challenges. We report here the geminal cross couplings of three components by reactions of dihaloalkanes with organomagnesium and chlorosilanes or alkyl tosylates by Cr catalysis, affording the formation of geminal C-C/C-Si or C-C/C-C bonds in the creation of tertiary and quaternary alkanes. The geminal couplings are catalyzed by low-cost CrCl2 , enabling the sluggishness of competitive Kumada-type side couplings and homocouplings of Grignard reagents, in achieving high chemoselectivity. Experimental and theoretical studies indicate that two geminal C-halide bonds are continuously cleaved by Cr to afford a metal carbene intermediate, which couples with a Grignard reagent, followed by silylation, in the formation of geminal C-C and C-Si bonds via a novel inner-sphere radical coupling mechanism. These three-component geminal cross couplings are value-addition to the synthesis of commercial drugs and bioactive molecules in medicinal chemistry.

Mechanistic Diversity of Low-Valent Chromium Catalysis: Cross-Coupling and Hydrofunctionalization.

ConspectusTransition-metal catalysis has traditionally been dominated by precious metals because of their high reactivity toward chemical transformations. As a cost-effective alternative, catalysis by earth-abundant group 6 metal chromium is underdeveloped, and its reactivity remains largely unexplored, although the industrially important Phillips catalyst, which is composed of Cr as the active metal, is currently used to supply almost 40% of the total world demand for high-density polyethylene. Cr has traditionally served in organoreagents with high-valent states (≥2+), which are typified by reactions involving Nozaki-Hiyama-Kishi (NHK) and Takai-Utimoto one-electron transfer processes. Given that low-valent metals usually facilitate the process of oxidative addition (OA), studying the catalysis of Cr in the low-valent state provides the opportunity to develop new transformations. However, probably because of the low stability of reactive low-valent Cr or the lack of catalytic activity of structurally stable complexes, there has been limited success with respect to developing catalysis promoted by low-valent Cr. In recent years, our group has probed the reactivity of low-valent Cr in catalysis by adopting a strategy of forming reactive Cr in situ. In this Account, we detail our efforts to study the catalytic behavior and mechanism of low-valent Cr in challenging transformations, such as the cleavage of chemically inert bonds for the cross-coupling and hydrofunctionalization of arenes and nitro motifs, by developing strategies to address the prominent selectivity issues. We highlight the finding that low-valent Cr, being formed in situ, possesses the intriguing ability to promote the catalytic cleavage of unactivated C-O, C-N, and C-H bonds to achieve the Kumada couplings and even to enable challenging cross-coupling between two unactivated C(aryl)-O/C(aryl)-N bonds. During these catalytic processes, Cr usually adopts a high-spin state to interact with chemicals, allowing for insertion into unactivated σ-bonds. The OA catalytic model involving a two-electron process for the cleavage of unactivated bonds has rarely been considered for Cr. We highlight the finding that Cr allows for the breakage of two chemically inert bonds in one catalytic cycle. This ability is intriguing because most transition metals are suitable only for the cleavage of one unactivated bond in catalysis. Mechanisms involving two-electron OA for Cr are unusual, with processes involving one-electron transfer more often proposed, as exemplified in the NHK reactions. These reactions provide efficient strategies for forming functionalized benzaldehydes, amides, anilines, and amines, usually with high levels of selectivity. We hope that this account will extend the scope of cognition to Cr catalysis.

Trends and Rural-Urban Differences in Participation in Diabetes Self-management Education Among Adults in North Carolina: 2012-2017.

PURPOSE: This study aimed to report recent trends in self-reported diabetes self-management education (DSME) participation rates among adults in North Carolina and to compare these rates between rural and urban residents. METHODS: Data for this analysis were obtained from the NC Behavioral Risk Factor Surveillance System (BRFSS) for the years 2012, 2013, 2015, and 2017, when the survey included the diabetes module. Respondents were classified as having participated in DSME if they answered "Yes" to the question, "Have you ever taken a course or class in how to manage your diabetes yourself?" We used the Rural Urban Continuum Code to classify urban and rural residence. The study sample included 4368 adults 18 years or older with self-reported diabetes. We assessed the changes in DSME participation from 2012 to 2017. We used multiple logistic regression modeling to assess the association between rural residence and DSME participation. All analyses were conducted in Stata 14 and accounted for the survey design of the BRFSS. Statistical significance was set at P < .01. RESULTS: Overall, the DSME participation rates decreased slightly in the study period, from 55.8% in 2012 to 55.6% in 2013 to 56.5% in 2015 to 52.1% in 2017. By rural-urban residence, the rates were 52.3% versus 57.8% in 2012, 54.0% versus 56.5% in 2013, 48.8% versus 62.0% in 2015, and 46.7% versus 56.1% in 2017. The multiple logistic regression model results showed that rural residents were less likely to have participated in DSME (adjusted odds ratio = 0.78; 95% confidence interval, 0.64-0.94) than urban residents. Adults with higher income and education levels were also more likely to have participated in DSME (P < .01). CONCLUSIONS: The recent BRFSS data showed that the DSME participation rate declined slightly in North Carolina. There were persistent rural-urban disparities in DSME participation, with rural residents showing lower rates, and the gaps seemed to be widening. IMPLICATIONS FOR POLICY OR PRACTICE: Continuous efforts are needed to bring more American Diabetes Association/American Association of Diabetes Educators programs to rural communities and assist persons with diabetes to participate in DSME training to reduce the burden of diabetes. Furthermore, those in rural areas may need additional support.

Telehealth: Reducing Patients' Greenhouse Gas Emissions at One Academic Psychiatry Department.

OBJECTIVE: Academic and organizational leaders in psychiatry and all other medical fields are negatively impacted by climate change. The COVID-19 pandemic prompted a rapid shift to the use of more telehealth by behavioral health clinicians. The purpose of this study was to estimate the reduction of patients' greenhouse gas emissions during this rapid shift at one academic psychiatry institution. METHODS: The authors extracted data associated with all outpatient visits to all 26 psychiatry clinics from March 16, 2020, to December 31, 2020. Once the patients' travel miles saved by confirmed virtual visits were calculated, the authors used the standard ratio from the US Environmental Protection Agency (EPA) to calculate the total quantity of CO2 that would be emitted if the visits had occurred in person. RESULTS: During the study period, a total of 47,582 outpatient behavioral health visits with 3975 unique patients were completed. The majority of these departmental visits were telehealth (85%), with most of the telehealth visits conducted using real-time audio-video platforms (75.7%). Subtracting emissions from patient technology during telehealth visits from the estimated patient transport values produced a net savings of greenhouse gas emissions of 867,011 kg CO2. This amount is equal to the greenhouse gas emissions from 189 passenger vehicles driven for 1 year according to the EPA. CONCLUSIONS: This study shows that converting in person, face-to-face behavioral health visits to telehealth has the potential to increase both energy efficiency and conservation through a reduction in greenhouse gas emissions due to reduced patient travel. If these values were extrapolated to the total adult US population who have visits for behavioral health reasons, we estimate that conversion to virtual visits could save approximately 830,000 metric tons of CO2 annually. Organizational leaders should consider these societal benefits when making decisions regarding development and support of telehealth.

Cyclic (Alkyl)(amino)carbene Ligand-Promoted Nitro Deoxygenative Hydroboration with Chromium Catalysis: Scope, Mechanism, and Applications.

Transition metal catalysis that utilizes N-heterocyclic carbenes as noninnocent ligands in promoting transformations has not been well studied. We report here a cyclic (alkyl)(amino)carbene (CAAC) ligand-promoted nitro deoxygenative hydroboration with cost-effective chromium catalysis. Using 1 mol % of CAAC-Cr precatalyst, the addition of HBpin to nitro scaffolds leads to deoxygenation, allowing for the retention of various reducible functionalities and the compatibility of sensitive groups toward hydroboration, thereby providing a mild, chemoselective, and facile strategy to form anilines, as well as heteroaryl and aliphatic amine derivatives, with broad scope and particularly high turnover numbers (up to 1.8 × 106). Mechanistic studies, based on theoretical calculations, indicate that the CAAC ligand plays an important role in promoting polarity reversal of hydride of HBpin; it serves as an H-shuttle to facilitate deoxygenative hydroboration. The preparation of several commercially available pharmaceuticals by means of this strategy highlights its potential application in medicinal chemistry.

Whole-exome sequencing identifies novel mutations in ABC transporter genes associated with intrahepatic cholestasis of pregnancy disease: a case-control study.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) can cause premature delivery and stillbirth. Previous studies have reported that mutations in ABC transporter genes strongly influence the transport of bile salts. However, to date, their effects are still largely elusive. METHODS: A whole-exome sequencing (WES) approach was used to detect novel variants. Rare novel exonic variants (minor allele frequencies: MAF < 1%) were analyzed. Three web-available tools, namely, SIFT, Mutation Taster and FATHMM, were used to predict protein damage. Protein structure modeling and comparisons between reference and modified protein structures were performed by SWISS-MODEL and Chimera 1.14rc, respectively. RESULTS: We detected a total of 2953 mutations in 44 ABC family transporter genes. When the MAF of loci was controlled in all databases at less than 0.01, 320 mutations were reserved for further analysis. Among these mutations, 42 were novel. We classified these loci into four groups (the damaging, probably damaging, possibly damaging, and neutral groups) according to the prediction results, of which 7 novel possible pathogenic mutations were identified that were located in known functional genes, including ABCB4 (Trp708Ter, Gly527Glu and Lys386Glu), ABCB11 (Gln1194Ter, Gln605Pro and Leu589Met) and ABCC2 (Ser1342Tyr), in the damaging group. New mutations in the first two genes were reported in our recent article. In addition, compared to the wild-type protein structure, the ABCC2 Ser1342Tyr-modified protein structure showed a slight change in the chemical bond lengths of ATP ligand-binding amino acid side chains. In placental tissue, the expression level of the ABCC2 gene in patients with ICP was significantly higher (P < 0.05) than that in healthy pregnant women. In particular, the patients with two mutations in ABC family genes had higher average values of total bile acids (TBA), aspartate transaminase (AST), direct bilirubin (DBIL), total cholesterol (CHOL), triglycerides (TG) and high-density lipoprotein (HDL) than the patients who had one mutation, no mutation in ABC genes and local controls. CONCLUSIONS: Our present study provide new insight into the genetic architecture of ICP and will benefit the final identification of the underlying mutations.

Reductive Cross-Coupling between Unactivated C(aryl)-N and C(aryl)-O Bonds by Chromium Catalysis Using a Bipyridyl Ligand.

Reductive cross-coupling between two chemically inert bonds remains a great challenge in synthetic chemistry. We report here the reductive cross-coupling between unactivated C(aryl)-N and C(aryl)-O bonds that was achieved by chromium catalysis. The simple and inexpensive CrCl2 salt, combined with important bipyridyl ligand and magnesium reductant, shows high reactivity in the successive cleavage of C(aryl)-N bonds of aniline derivatives and C(aryl)-O bonds of aryl esters, allowing the cross-coupling of these two unactivated and different bonds to occur in a reductive fashion to form a C(aryl)-C(aryl) bond. Mechanistic studies by deuterium-labeling experiments indicate that the C(aryl)-N bonds in anilines are preferentially cleaved by reactive Cr species, in which the ligation of bipyridyl with Cr by adopting a coordination model in 1:1 ratio can be considered.

Chemoselective Cross-Coupling between Two Different and Unactivated C(aryl)-O Bonds Enabled by Chromium Catalysis.

We report here the first example of cross-coupling between two different and unactivated C(aryl)-O bonds with chromium catalysis. The combination of a low-cost Cr(II) salt, 4,4'-di-tert-butyl-2,2'-dipyridyl (dtbpy) as the ligand, and magnesium as the reductant shows high reactivity in promoting the reductive cross-coupling of aryl methyl ether derivatives with aryl esters by cleavage and coupling of two different C(aryl)-O bonds under mild conditions. The formation of active low-valent Cr species by reduction of CrCl2 with Mg can be considered, which prefers to initially activate the C(aryl)-O bond of phenyl methyl ether with the chelation help of dtbpy and an o-imine auxiliary. The subsequent consecutive reduction, second C(aryl)-O activation, and reductive elimination allow for the achievement of selective cross-coupling of C(aryl)-O/C(aryl)-O bonds.

Whole-exome sequencing reveals ANO8 as a genetic risk factor for intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and cholestasis in late pregnancy and results in adverse pregnancy outcomes, including preterm delivery and birth weight, which are affected by the genetic and environmental background. However, until now, the genetic architecture of ICP has remained largely unclear. METHODS: Twenty-six clinical data points were recorded for 151 Chinese ICP patients. The data generated from whole-exome sequencing (WES) using the BGISEQ-500 platform were further analyzed by Burrows-Wheeler Aligner (BWA) software, Genome Analysis Toolkit (GATK), ANNOVAR tool, etc. R packages were used to conduct t-test, Fisher's test and receiver operating characteristic (ROC) curve analyses. RESULTS: We identified eighteen possible pathogenic loci associated with ICP disease in known genes, covering ABCB4, ABCB11, ATP8B1 and TJP2. The loci Lys386Gln, Gly527Gln and Trp708Ter in ABCB4, Leu589Met, Gln605Pro and Gln1194Ter in ABCB11, and Arg189Ser in TJP2 were novel discoveries. In addition, WES analysis indicated that the gene ANO8 involved in the transport of bile salts is newly identified as associated with ICP. The functional network of the ANO8 gene confirmed this finding. ANO8 contained 8 rare missense mutations that were found in eight patients among the 151 cases and were absent from 1029 controls. Out of the eight SNPs, 3 were known, and the remaining five are newly identified. These variants have a low frequency, ranging from 0.000008 to 0.00001 in the ExAC, gnomAD - Genomes and TOPMED databases. Bioinformatics analysis showed that the sites and their corresponding amino acids were both highly conserved among vertebrates. Moreover, the influences of all the mutations on protein function were predicted to be damaging by the SIFT tool. Combining clinical data, it was found that the mutation group (93.36 µmol/L) had significantly (P = 0.038) higher total bile acid (TBA) levels than the wild-type group (40.81 µmol/L). CONCLUSIONS: To the best of our knowledge, this is the first study to employ WES technology to detect genetic loci for ICP. Our results provide new insights into the genetic basis of ICP and will benefit the final identification of the underlying mutations.

Chromium- and Cobalt-Catalyzed, Regiocontrolled Hydrogenation of Polycyclic Aromatic Hydrocarbons: A Combined Experimental and Theoretical Study.

Polycyclic aromatic hydrocarbons are difficult substrates for hydrogenation because of the thermodynamic stability caused by aromaticity. We report here the first chromium- and cobalt-catalyzed, regiocontrolled hydrogenation of polycyclic aromatic hydrocarbons at ambient temperature. These reactions were promoted by low-cost chromium or cobalt salts combined with diimino/carbene ligand and methylmagnesium bromide and are characterized by high regioselectivity and expanded substrate scope that includes tetracene, tetraphene, pentacene, and perylene, which have rarely been reduced. The approach provides a cost-effective catalytic protocol for hydrogenation, is scalable, and can be utilized in the synthesis of tetrabromo- and carboxyl-substituted motifs through functionalization of the hydrogenation product. The systematic theoretical mechanistic modelings suggest that low-valent Cr and Co monohydride species, most likely from zerovalent transition metals, are capable of mediating these hydrogenations of fused PAHs.

A Blockchain Framework for Patient-Centered Health Records and Exchange (HealthChain): Evaluation and Proof-of-Concept Study.

BACKGROUND: Blockchain has the potential to disrupt the current modes of patient data access, accumulation, contribution, exchange, and control. Using interoperability standards, smart contracts, and cryptographic identities, patients can securely exchange data with providers and regulate access. The resulting comprehensive, longitudinal medical records can significantly improve the cost and quality of patient care for individuals and populations alike. OBJECTIVE: This work presents HealthChain, a novel patient-centered blockchain framework. The intent is to bolster patient engagement, data curation, and regulated dissemination of accumulated information in a secure, interoperable environment. A mixed-block blockchain is proposed to support immutable logging and redactable patient blocks. Patient data are generated and exchanged through Health Level-7 Fast Healthcare Interoperability Resources, allowing seamless transfer with compliant systems. In addition, patients receive cryptographic identities in the form of public and private key pairs. Public keys are stored in the blockchain and are suitable for securing and verifying transactions. Furthermore, the envisaged system uses proxy re-encryption (PRE) to share information through revocable, smart contracts, ensuring the preservation of privacy and confidentiality. Finally, several PRE improvements are offered to enhance performance and security. METHODS: The framework was formulated to address key barriers to blockchain adoption in health care, namely, information security, interoperability, data integrity, identity validation, and scalability. It supports 16 configurations through the manipulation of 4 modes. An open-source, proof-of-concept tool was developed to evaluate the performance of the novel patient block components and system configurations. To demonstrate the utility of the proposed framework and evaluate resource consumption, extensive testing was performed on each of the 16 configurations over a variety of scenarios involving a variable number of existing and imported records. RESULTS: The results indicate several clear high-performing, low-bandwidth configurations, although they are not the strongest cryptographically. Of the strongest models, one's anticipated cumulative record size is shown to influence the selection. Although the most efficient algorithm is ultimately user specific, Advanced Encryption Standard-encrypted data with static keys, incremental server storage, and no additional server-side encryption are the fastest and least bandwidth intensive, whereas proxy re-encrypted data with dynamic keys, incremental server storage, and additional server-side encryption are the best performing of the strongest configurations. CONCLUSIONS: Blockchain is a potent and viable technology for patient-centered access to and exchange of health information. By integrating a structured, interoperable design with patient-accumulated and generated data shared through smart contracts into a universally accessible blockchain, HealthChain presents patients and providers with access to consistent and comprehensive medical records. Challenges addressed include data security, interoperability, block storage, and patient-administered data access, with several configurations emerging for further consideration regarding speed and security.

Hydrogenation of (Hetero)aryl Boronate Esters with a Cyclic (Alkyl)(amino)carbene-Rhodium Complex: Direct Access to cis-Substituted Borylated Cycloalkanes and Saturated Heterocycles.

We herein report the hydrogenation of substituted aryl- and heteroaryl boronate esters for the selective synthesis of cis-substituted borylated cycloalkanes and saturated heterocycles. A cyclic (alkyl)(amino)carbene-ligated rhodium complex with two dimethyl groups at the ortho-alkyl scaffold of the carbene showed high reactivity in promoting the hydrogenation, thereby enabling the hydrogenation of (hetero)arenes with retention of the synthetically valuable boronate group. This process constitutes a clean, atom-economic, as well as chemo- and stereoselective route for the generation of cis-configured, diversely substituted borylated cycloalkanes and saturated heterocycles that are usually elusive and difficult to prepare.