bluuebunny/crossref_metadata_2025 huggingface dataset:
Judicial avoidance at the European Court of Human Rights: Institutional authority, the procedural turn, and docket control
Authors: Jackson Miles
Published: February 2022

This article concerns the ongoing conflict over the authority of the European Court of Human Rights (ECtHR). As has been widely discussed, the authority of the Court has come under sustained pressure from states over the last decade. As one response to this pressure, the Court has undertaken what the literature calls a procedural turn—a doctrinal shift that has incorporated its changing political dynamic into its case law. The procedural turn is constituted by renewed deference to national authorities “premised on good faith domestic engagement with [European Convention on Human Rights] principles.” This article sets out a functional critique of the procedural turn by drawing attention to certain limitations in its assumptions and application. Is there an alternative—or additional—way for the Court to respond? Drawing on the practice of other courts, I propose that the ECtHR take seriously judicial avoidance as a way to protect its authority—specifically, the Court might avoid making a determination of a particular case at a particular time. This approach—though not without objection—may provide the Court with an ad hoc, flexible capacity to protect its authority, and comes with the additional benefits of neither legitimating the underlying domestic measure nor upsetting important doctrinal structures relevant to other cases. I further suggest that control of its docket through introducing strategic considerations at the admissibility stage would be the most appropriate technique of avoidance for the Court.
Living With Stigma and Low Self-esteem Among Individuals With Burn Injuries: A Cross-sectional Study
Authors: Wu Xiaoxue , Hu Yueyun , Hu Ailing
Published: February 2022

Burn injuries are a significant global public health concern. The psychological problems deserve more attention. Research has shown that reducing the stigma and improving the burn patient’s self-esteem are effective means to promote social reintegration. The aim of this study is to explore the relationship between stigma and self-esteem and to examine the independent factors that contribute to with the stigma of burns. The convenience sampling method was used in Guangzhou, China. A cross-sectional study was conducted using the Social Impact Scale, Rosenberg Self-Esteem Scale, and a sociodemographic questionnaire. Descriptive statistics, statistical inference, correlation testing, and regression analysis were used to analyze the data among 146 burn survivors. The P-value was set as .05. The mean score of SIS was 57.03 ± 6.762. Of the four components of the Social Impact Scale, social rejection had the highest mean score (21.72 ± 3.00). The mean Self-Esteem Scale score was 21.05 ± 2.492, markedly different from the general population. A moderate positive correlation (r = .546, P < .001) was found between stigma and low self-esteem among burn victims. Multiple linear regression analysis identified residence, itching, and Self-Esteem Scale score as significant influencing factors, accounting for 38.5% of the total variance in stigma. Burn survivors reported moderate levels of stigma and low levels of self-esteem. Residence, itching, and Self-Esteem Scale score were significant influencing factors for stigma. To promote recovery of patients with burn injury, it is necessary to eliminate the stigma and improve their self-esteem.
Hemispheric Asymmetry and Atypical Lobar Progression of Alzheimer-Type Tauopathy
Authors: Tremblay Cécilia , Serrano Geidy E , Intorcia Anthony J , Curry Jasmine , Sue Lucia I , Nelson Courtney M , Walker Jessica E , Glass Michael J , Arce Richard A , Fleisher Adam S , Pontecorvo Michael J , Atri Alireza , Montine Thomas J , Chen Kewei , Beach Thomas G
Published: February 2022

The spread of neurofibrillary tau pathology in Alzheimer disease (AD) mostly follows a stereotypical pattern of topographical progression but atypical patterns associated with interhemispheric asymmetry have been described. Because histopathological studies that used bilateral sampling are limited, this study aimed to assess interhemispheric tau pathology differences and the presence of topographically atypical cortical spreading patterns. Immunohistochemical staining for detection of tau pathology was performed in 23 regions of interest in 57 autopsy cases comparing bilateral cortical regions and hemispheres. Frequent mild (82% of cases) and occasional moderate (32%) interhemispheric density discrepancies were observed, whereas marked discrepancies were uncommon (7%) and restricted to occipital regions. Left and right hemispheric tau pathology dominance was observed with similar frequencies, except in Braak Stage VI that favored a left dominance. Interhemispheric Braak stage differences were observed in 16% of cases and were more frequent in advanced (IV–VI) versus early (I–III) stages. One atypical lobar topographical pattern in which occipital tau pathology density exceeded frontal lobe scores was identified in 4 cases favoring a left dominant asymmetry. We speculate that asymmetry and atypical topographical progression patterns may be associated with atypical AD clinical presentations and progression characteristics, which should be tested by comprehensive clinicopathological correlations.
USDA Forest Service Employee Diversity During a Period of Workforce Contraction
Authors: Westphal Lynne M , Dockry Michael J , Kenefic Laura S , Sachdeva Sonya S , Rhodeland Amelia , Locke Dexter H , Kern Christel C , Huber-Stearns Heidi R , Coughlan Michael R
Published: February 2022

We analyzed USDA Forest Service (Forest Service) employment data from 1995 to 2017, by race and ethnicity, gender, as well as race/ethnicity and gender, to assess progress towards the Forest Service’s goal of achieving a multicultural workforce that reflects the US population. We look at the trends by an employee’s level in the Forest Service and by branch of the Forest Service. Our data show an overall decrease in the workforce by nearly 20%, an increase in diversity in Forest Service leadership levels, little change in the percentage of employees in non-White racial/ethnic groups combined, the number of Black employees decreased, and the number of women in lower grades and in the National Forest System Deputy Area decreased. Comparison with the civilian labor force provides additional context. Implications are relevant beyond the Forest Service, including a risk of losing public trust and reduced agency effectiveness if a representative workforce is not achieved.
5-Amino-4-Imidazolecarboxamide Ribonucleotide Transformylase/IMP Cyclohydrolase Polymorphisms Affect the Susceptibility to Multiple Myeloma
Authors: Wang Yu , Ling Zhian , Hu Zuojian , Gui Ying , Huang Chunni , Yao Yibin , Li Ruolin
Published: February 2022

Objective

The upregulation of 5-amino-4-imidazolecarboxamide ribonucleotide transformylase/IMP cyclohydrolase (ATIC) may affect tumorigenesis and multiple myeloma (MM) development.

Materials and Methods

A total of 97 patients with MM and 102 healthy control patients were included in the study. The SNaPshot technique was used to detect the ATIC gene polymorphisms. Linkage disequilibrium (LD) and haplotype analyses were conducted using SHEsis software.

Results

The genotype distribution or allele frequency of rs3772078 and rs16853834 was significantly different between the patients with MM and the healthy control patients (all P < .05). The rs16853834 A allele, rs3772078 CT genotype, and C allele were associated with a decreased risk of MM (all P < .05). Five single-nucleotide polymorphism combinations showed strong LD. Three haplotypes were associated with MM risk (all P < .05). We found that ATIC rs7604984 was significantly associated with serum lactate dehydrogenase levels (P = .050).

Conclusion

We determined that the rs3772078 and rs16853834 polymorphisms are associated with a decreased risk of MM.
UV/VUV photoprocessing of protonatedN-hetero(poly)acenes
Authors: Jacovella Ugo , Hansen Christopher S , Giuliani Alexandre , Trevitt Adam J , Nahon Laurent
Published: February 2022

N-heterocycles are suspected to play an important role in the chemical origin of life. Despite their detection in meteorites and in Titan’s atmosphere, their extra-terrestrial chemical formation networks remain elusive. Furthermore N-heterocyclics are undetected in the interstellar medium. This paper assesses the photostability of protonated N-hetero(poly)acenes after ultraviolet (UV) and vacuum ultraviolet (VUV) excitation. It provides information on their ability to retain the N atom into the cycle to generate larger N-containing species or functionalized N-heterocyles. Protonated N-hetero(poly)acenes were generated using electrospray ionization and injected into a linear ion trap where they were irradiated by radiation of 4.5 to 10 eV using the DESIRS beamline at the synchrotron SOLEIL. The photodissociation action spectra of protonated pyridine, quinoline, isoquinoline, and acridine were measured by recording the photofragment yields as a function of photon energy. The four systems exhibit dissociation channels associated with H2 and HCN/HNC loss but with different branching ratios. The results indicate that increasing the size of the N-hetero(poly)acenes increases the chance of retaining the N atom in the larger fragment ion after photodissociation but it remains that all the protonated N-hetero(poly)acenes studied lose their N atom at part of a small neutral photofragment, with high propensity. Therefore, protonated N-hetero(poly)acenes in interstellar space are unlikely precursors to form larger N-containing species. However, protonated pyridine, quinoline, isoquinoline, and acridine are most likely to retain their N atoms in planetary atmospheres where UV radiation at the planet’s surface is typically restricted to wavelengths greater than 200 nm – suggesting such environments are possible substrates for prebiotic chemistry.
The column densities of molecular gas across cosmic time: bridging observations and simulations
Authors: Szakacs Roland , Péroux Céline , Zwaan Martin A , Nelson Dylan , Schinnerer Eva , Lahén Natalia , Weng Simon , Fresco Alejandra Y
Published: February 2022

Observations of the cosmic evolution of different gas phases across time indicate a marked increase in the molecular gas mass density towards z ∼ 2–3. Such a transformation implies an accompanied change in the global distribution of molecular hydrogen column densities ($N_{\rm {H_2}}$). Using observations by PHANGS-ALMA/SDSS and simulations by GRIFFIN/IllustrisTNG we explore the evolution of this H2 column density distribution function [$f(N_{\rm {H}_2})$]. The H2 (and H i) column density maps for TNG50 and TNG100 are derived in post-processing and are made available through the IllustrisTNG online API. The shape and normalization of $f(N_{\rm {H}_2})$ of individual main-sequence star-forming galaxies are correlated with the star formation rate (SFR), stellar mass (M*), and H2 mass ($M_{\rm {H}_2}$) in both observations and simulations. TNG100, combined with H2 post-processing models, broadly reproduces observations, albeit with differences in slope and normalization. Also, an analytically modelled f(N), based on exponential gas discs, matches well with the simulations. The GRIFFIN simulation gives first indications that the slope of $f(N_{\rm {H}_2})$ might not majorly differ when including non-equilibrium chemistry in simulations. The $f(N_{\rm {H}_2})$ by TNG100 implies that higher molecular gas column densities are reached at z = 3 than at z = 0. Further, denser regions contribute more to the molecular mass density at z = 3. Finally, H2 starts dominating compared to H i only at column densities above log($N_{\rm {H}_2} / \rm {cm}^{-2}) \sim 21.8\!-\!22$ at both redshifts. These results imply that neutral atomic gas is an important contributor to the overall cold gas mass found in the ISM of galaxies including at densities typical for molecular clouds at z = 0 and 3.
KiDS-1000 cosmology: machine learning – accelerated constraints on interacting dark energy with CosmoPower
Authors: Spurio Mancini A , Pourtsidou A
Published: February 2022

We derive constraints on a coupled quintessence model with pure momentum exchange from the public ∼1000 deg2 cosmic shear measurements from the Kilo-Degree Survey and the Planck 2018 cosmic microwave background data. We compare this model with Lambda cold dark matter and find similar χ2 and log-evidence values. We accelerate parameter estimation by sourcing cosmological power spectra from the neural network emulator CosmoPower. We highlight the necessity of such emulator-based approaches to reduce the computational runtime of future similar analyses, particularly from Stage IV surveys. As an example, we present Markov Chain Monte Carlo forecasts on the same coupled quintessence model for a Euclid-like survey, revealing degeneracies between the coupled quintessence parameters and the baryonic feedback and intrinsic alignment parameters, but also highlighting the large increase in constraining power Stage IV surveys will achieve. The contours are obtained in a few hours with CosmoPower, as opposed to the few months required with a Boltzmann code.
Acute Dacryoadenitis due to Primary Epstein-Barr Virus Infection
Authors: Hayano Satoshi , Nakada Naruhiko , Kashima Masayuki
Published: February 2022

We herein present the case of a 28-year-old male patient who presented with fever and bilateral upper eyelid edema without other upper airway symptoms and was diagnosed with acute dacryoadenitis due to Epstein-Barr virus (EBV) infection. The patient’s medical history was unremarkable. Laboratory tests revealed lymphocytosis with atypical lymphocytes and abnormal liver function tests. Physical examination and computed tomography revealed swelling in the lacrimal glands, and serological tests confirmed EBV infection. Although rare, ocular symptoms of primary EBV infection are important for diagnosis. Acute dacryoadenitis should be considered as a rare manifestation and an underdiagnosed complication of primary EBV infection.
Overexpression of IGF-1 During Early Development Expands the Number of Mammary Stem Cells and Primes them for Transformation
Authors: Luo Linjie , Santos Andres , Konganti Kranti , Hillhouse Andrew , Lambertz Isabel U , Zheng Yuanning , Gunaratna Ramesh T , Threadgill David W , Fuchs-Young Robin S
Published: February 2022

Insulin-like growth factor I (IGF-1) has been implicated in breast cancer due to its mitogenic and anti-apoptotic effects. Despite substantial research on the role of IGF-1 in tumor progression, the relationship of IGF-1 to tissue stem cells, particularly in mammary tissue, and the resulting tumor susceptibility has not been elucidated. Previous studies with the BK5.IGF-1 transgenic (Tg) mouse model reveals that IGF-1 does not act as a classical, post-carcinogen tumor promoter in the mammary gland. Pre-pubertal Tg mammary glands display increased numbers and enlarged sizes of terminal end buds, a niche for mammary stem cells (MaSCs). Here we show that MaSCs from both wild-type (WT) and Tg mice expressed IGF-1R and that overexpression of Tg IGF-1 increased numbers of MaSCs by undergoing symmetric division, resulting in an expansion of the MaSC and luminal progenitor (LP) compartments in pre-pubertal female mice. This expansion was maintained post-pubertally and validated by mammosphere assays in vitro and transplantation assays in vivo. The addition of recombinant IGF-1 promoted, and IGF-1R downstream inhibitors decreased mammosphere formation. Single-cell transcriptomic profiles generated from 2 related platforms reveal that IGF-1 stimulated quiescent MaSCs to enter the cell cycle and increased their expression of genes involved in proliferation, plasticity, tumorigenesis, invasion, and metastasis. This study identifies a novel, pro-tumorigenic mechanism, where IGF-1 increases the number of transformation-susceptible carcinogen targets during the early stages of mammary tissue development, and “primes” their gene expression profiles for transformation.
Chronic Hexavalent Chromium Exposure Upregulates the RNA Methyltransferase METTL3 Expression to Promote Cell Transformation, Cancer Stem Cell-Like Property, and Tumorigenesis
Authors: Wang Zhishan , Uddin Mohammad Burhan , Xie Jie , Tao Hua , Zeidler-Erdely Patti C , Kondo Kazuya , Yang Chengfeng
Published: February 2022

Hexavalent chromium [Cr(VI)] is a common environmental carcinogen causing lung cancer in humans. This study investigates the mechanism of Cr(VI) carcinogenesis focusing on the role of the epitranscriptomic dysregulation. The epitranscriptomic effect of Cr(VI) was determined in Cr(VI)-transformed human bronchial epithelial cells, chromate-exposed mouse and human lungs. The epitranscriptomic effect and its role in Cr(VI)-induced cell transformation, cancer stem cell (CSC)-like property, and tumorigenesis were determined by microarray analysis, soft agar colony formation, suspension spheroid formation, and mouse xenograft tumorigenesis assays. It was found that chronic Cr(VI) exposure causes epitranscriptomic dysregulations as evidenced by the increased levels of total RNA N6-methyladenosine (m6A) modification and the RNA m6A methyltransferase like-3 (METTL3) in Cr(VI)-transformed cells and chromate exposure-caused mouse and human lung tumors. Knockdown of METTL3 expression in Cr(VI)-transformed cells significantly reduces their m6A levels and transformed phenotypes and tumorigenicity in mice. Moreover, knockdown of METTL3 expression in parental nontransformed cells significantly reduces the capability of chronic Cr(VI) exposure to induce cell transformation and CSC-like property. Together, this study reveals that chronic Cr(VI) exposure is capable of altering cellular epitranscriptome by increasing the m6A RNA modification via upregulating the RNA methyltransferase METTL3 expression, which plays an important role in Cr(VI)-induced cell transformation, CSC-like property, and tumorigenesis.
Metabolites of Synthetic Cannabinoid 5F-MDMB-PINACA Retain Affinity, Act as High Efficacy Agonists and Exhibit Atypical Pharmacodynamic Properties at CB1 Receptors
Authors: Cabanlong Christian V , Russell Lauren N , Fantegrossi William E , Prather Paul L
Published: February 2022

Synthetic cannabinoid receptor agonists (SCRAs) are a large group of abused psychoactive compounds that elicit numerous toxic effects not observed with cannabis, including death. Abuse of third-generation SCRA 5F-MDMB-PINACA (also known as 5F-ADB) has been associated with over 40 fatalities. This SCRA is metabolized to several active phase I metabolites, including excessively high post-mortem serum concentrations of an ester hydrolysis metabolite, 5F-MDMB-PINACA-M7 (M7). Although high serum concentrations of M7 (and other active metabolites) have been suggested to contribute to 5F-MDMB-PINACA toxicity, the affinity of M7 for CB1 receptors is unknown and more complete pharmacodynamic characterization of 5F-MDMB-PINACA and its active metabolites is needed. Competition binding and G-protein modulation studies presented here confirm reports that 5F-MDMB-PINACA and a second N-5-hydroxypentyl metabolite (M2) exhibit nM affinity and act as high efficacy agonists at CB1 receptors. Also as previously published, M7 exhibits high efficacy at CB1 receptors; however, demonstrated here for the first time, M7 retains only low μΜ affinity. Empirically derived Kb values indicate rimonabant differentially antagonizes G-protein activation produced by 5F-MDMB-PINACA, relative to Δ9-THC (THC) or its metabolites. Chronic administration of 5F-MDMB-PINACA and metabolites results in CB1 down-regulation, but only 5F-MDMB-PINACA produces desensitization. Although low CB1 affinity/potency of M7 precluded in vivo studies, both M2 and THC produce locomotor suppression and CB1-mediated dose-dependent hypothermia and analgesia in mice. Collectively, these data confirm and extend previous studies suggesting that 5F-MDMB-PINACA is metabolized to active compounds exhibiting atypical pharmacodynamic properties at CB1 receptors, that may accumulate with parent drug to produce severe toxicity.
A strikingly ornamented fossil alligator lizard (Squamata:Abronia) from the Miocene of California
Authors: Scarpetta Simon G , Ledesma David T
Published: February 2022

Extant alligator lizards of the genus Abronia are found in montane cloud forests and pine-oak forests of Mesoamerica and are iconic among the public and scientific communities. Here, we describe a fossilized partial skull from the Miocene of southern California (~12.5–11.0 Mya) that is the first definitive fossil and only recognized extinct species of Abronia. The locality of the fossil is substantially removed from the range of extant species of Abronia. This remarkable biogeographical discovery corroborates previous speculation that Abronia was distributed north of Mexico during the Neogene, a scenario that could not be inferred from the geographical ranges and phylogeny of the extant species alone. Additionally, the fossil preserves a distinctive morphology, osteoderm sails, that appears unique to the new taxon among alligator lizards. The finding emphasizes the importance of the fossil record for historical biogeography and could motivate new avenues of biogeographical research in Mesoamerica and the USA.
Review of pediatric hypercarbia and intraoperative management
Authors: Evans Beata , Dore Seamas , Couser Deanna
Published: February 2022

Purpose of review

Hypercarbia in pediatric patients is an important component of intraoperative management. Despite marked advances in medicine and technology, it is uncertain what the physiological CO2 range in neonates, infants and small children. This data is extrapolated from the adult population. We are going to review advantages and disadvantages of CO2 measurement techniques, causes and systemic effects of hypercarbia. We are going to discuss how to approach management of intraoperative hypercarbia.

Recent findings

Although physiological range in this patient population may not be fully understood, it is known that any rapid change from a child's baseline increases risks of complications. Any derangements in CO2 are further compromised by hypoxia, hypotension, hypothermia, anemia, all of which may occur in a dynamic operating room environment.

Pediatric anesthesiologists and their teams must remain vigilant and anticipate these developments. Care must be taken to avoid any rapid changes in these vulnerable patients to minimize risks of adverse outcomes.
Extubation of the potentially difficult airway in the intensive care unit
Authors: Joffe Aaron , Barnes Christopher R.
Published: February 2022

Purpose of review

Extubation in the intensive care unit (ICU) is associated with a failure rate requiring reintubation in 10–20% patients further associated with significant morbidity and mortality. This review serves to highlight recent advancements and guidance on approaching extubation for patients at risk for difficult or failed extubation (DFE).

Recent findings

Recent literature including closed claim analysis, meta-analyses, and national society guidelines demonstrate that extubation in the ICU remains an at-risk time for patients. Identifiable strategies aimed at optimizing respiratory mechanics, patient comorbidities, and airway protection, as well as preparing an extubation strategy have been described as potential methods to decrease occurrence of DFE.

Extubation in the ICU remains an elective decision and patients found to be at risk should be further optimized and planning undertaken prior to proceeding. Extubation for the at-risk patient should be operationalized utilizing easily reproducible strategies, with airway experts present to guide decision making and assist in reintubation if needed.
Labor Market Attachment 2 Years After Colorectal Cancer Surgery
Authors: Juul Therese , Laurberg Søren , Andersen Niels T. , Nielsen Claus V. , Maribo Thomas , Emmertsen Katrine J. , Pedersen Pernille
Published: February 2022

Objectives:

To investigate the association between clinical/sociodemographic factors and labor market attachment, and to estimate employment probability 2 years after colorectal cancer (CRC) surgery.

Background:

A rising prevalence of younger CRC survivors commands a stronger focus on labor market attachment. The association between clinical factors like type of surgery and CRC survivors’ labor market attachment remains poorly investigated.

Methods:

National registries provided information on employment status and clinical/sociodemographic variables for all 20- to 60-year-old CRC patients without previous cancer diagnosed in Denmark from 2001 to 2014, undergoing surgery and being attached to the labor market. Associations between clinical/sociodemographic factors and labor market attachment were investigated in multiple logistic regression analyses.

Results:

A total of 5755 CRC patients were included. Two years after surgery, 59.7% were working. Factors significantly associated with a higher probability of working were being in the 46 to 50 years age group, male gender, higher educational level, no comorbidity, working at the time of diagnosis, lower Union for International Cancer Control stage, and undergoing surgery in the most recent of four time-periods. Two years after undergoing surgery, the probability of working was significantly higher for left-sided than for right-sided colon resections, higher for low anterior resection (LAR)/high tumor than for LAR/low tumor, and higher for abdominoperineal resection than for Hartmann’s procedure. Of the 4798 (86.8%) patients alive 2 years after surgery, 68.8% were working, 7.8% had retired, whereas 23.4% were on temporary benefits, sick leave, or disability pension.

Conclusions:

Clinical/sociodemographic factors were associated with the probability of working 2 years after surgery. This knowledge can be used to inform patients and target interventions towards patients with low post-CRC probability of working.
Tidal Volume–Dependent Activation of the Renin-Angiotensin System in Experimental Ventilator-Induced Lung Injury*
Authors: Mao Xinjun , Krenn Katharina , Tripp Thomas , Tretter Verena , Reindl-Schwaighofer Roman , Kraft Felix , Podesser Bruno K. , Zhu Yi , Poglitsch Marko , Domenig Oliver , Abraham Dietmar , Ullrich Roman
Published: February 2022

OBJECTIVES:

Ventilator-induced lung injury (VILI) is a major contributor to morbidity and mortality in critically ill patients. Mechanical damage to the lungs is potentially aggravated by the activation of the renin-angiotensin system (RAS). This article describes RAS activation profiles in VILI and discusses the effects of angiotensin (Ang) 1–7 supplementation or angiotensin-converting enzyme (ACE) inhibition with captopril as protective strategies.

DESIGN:

Animal study.

SETTING:

University research laboratory.

SUBJECTS:

C57BL/6 mice.

INTERVENTIONS:

Anesthetized mice (n = 12–18 per group) were mechanically ventilated with low tidal volume (LVT, 6 mL/kg), high tidal volume (HVT, 15 mL/kg), or very high tidal volume (VHVT, 30 mL/kg) for 4 hours, or killed after 3 minutes (sham). Additional VHVT groups received infusions of 60 μg/kg/hr Ang 1–7 or a single dose of 100 mg/kg captopril.

MEASUREMENTS AND MAIN RESULTS:

VILI was characterized by increased bronchoalveolar lavage fluid levels of interleukin (IL)-6, keratinocyte-derived cytokine, and macrophage inflammatory protein-2 (MIP2). The Ang metabolites in plasma measured with liquid chromatography tandem mass spectrometry showed a strong activation of the classical (Ang I, Ang II) and alternative RAS (Ang 1–7, Ang 1–5), with highest concentrations found in the HVT group. Although the lung-tissue ACE messenger RNA expression was unchanged, its protein expression showed a dose-dependent increase under mechanical ventilation. The ACE2 messenger RNA expression decreased in all ventilated groups, whereas ACE2 protein levels remained unchanged. Both captopril and Ang 1–7 led to markedly increased Ang 1–7 plasma levels, decreased Ang II levels, and ACE activity (Ang II/Ang I ratio), and effectively prevented VILI.

CONCLUSIONS:

VILI is accompanied by a strong activation of the RAS. Based on circulating Ang metabolite levels and tissue expression of RAS enzymes, classical ACE-dependent and alternative RAS cascades were activated in the HVT group, whereas classical RAS activation prevailed with VHVT ventilation. Ang 1–7 or captopril protected from VILI primarily by modifying the systemic RAS profile.
Etiology, Treatments, and Outcomes of Patients With Severe Community-Acquired Pneumonia in a Large U.S. Sample*
Authors: Haessler Sarah , Guo Ning , Deshpande Abhishek , Zilberberg Marya D. , Lagu Tara , Lindenauer Peter K. , Imrey Peter B. , Rothberg Michael B.
Published: February 2022

OBJECTIVES:

Compare the clinical practice and outcomes in severe community-acquired pneumonia (sCAP) patients to those in non-sCAP patients using guideline-defined criteria for sCAP.

DESIGN:

Retrospective observational cohort study.

SETTING:

One hundred seventy-seven U.S. hospitals within the Premier Healthcare Database.

PATIENTS:

Hospitalized adult (≥ 18 yr old) patients with pneumonia.

MEASUREMENTS AND MAIN RESULTS:

Adult patients (≥ 18 yr old) with a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia paired with a principal diagnosis of sepsis or respiratory failure were included. Patients with at least one guideline-defined major criterion for severe pneumonia were compared with patients with nonsevere disease. Among 154,799 patients with pneumonia, 21,805 (14.1%) met criteria for sCAP. They had higher organ failure scores (1.9 vs 0.63; p < 0.001) and inpatient mortality (22.0 vs 5.0%; p < 0.001), longer lengths of stay (8 vs 5 d; p < 0.001), and higher costs ($20,046 vs $7,543; p < 0.001) than those with nonsevere disease. Patients with sCAP had twice the rate of positive blood cultures (10.0% vs 4.5%; p < 0.001) and respiratory cultures (34.2 vs 21.1%; p < 0.001) and more often had isolates resistant to first-line community-acquired pneumonia antibiotics (10% of severe vs 3.1% of nonsevere; p < 0.001). Regardless of disease severity, Streptococcus pneumoniae was the most common pathogen recovered from blood cultures and Staphylococcus aureus and Pseudomonas species were the most common pathogens recovered from the respiratory tract. Although few patients with sCAP had cultures positive for a resistant organism, 65% received vancomycin and 42.8% received piperacillin-tazobactam.

CONCLUSIONS:

sCAP patients had worse outcomes and twice the rate of culture positivity. S. aureus and S. pneumoniae were the most common organisms in respiratory and blood specimens, respectively. Although only recommended for sCAP patients, nearly all pneumonia patients received blood cultures, a quarter of nonsevere patients received sputum cultures, and treatment with broad-spectrum agents was widespread, indicating fertile ground for antimicrobial and diagnostic stewardship programs.
Multimorbidity patterns and association with mortality in 0.5 million Chinese adults
Authors: Fan Junning , Sun Zhijia , Yu Canqing , Guo Yu , Pei Pei , Yang Ling , Chen Yiping , Du Huaidong , Sun Dianjianyi , Pang Yuanjie , Zhang Jun , Gilbert Simon , Avery Daniel , Chen Junshi , Chen Zhengming , Lyu Jun , Li Liming
Published: February 2022

Background:

Few studies have assessed the relationship between multimorbidity patterns and mortality risk in the Chinese population. We aimed to identify multimorbidity patterns and examined the associations of multimorbidity patterns and the number of chronic diseases with the risk of mortality among Chinese middle-aged and older adults.

Methods:

We used data from the China Kadoorie Biobank and included 512,723 participants aged 30 to 79 years. Multimorbidity was defined as the presence of two or more of the 15 chronic diseases collected by self-report or physical examination at baseline. Multimorbidity patterns were identified using hierarchical cluster analysis. Cox regression was used to estimate the associations of multimorbidity patterns and the number of chronic diseases with all-cause and cause-specific mortality.

Results:

Overall, 15.8% of participants had multimorbidity. The prevalence of multimorbidity increased with age and was higher in urban than rural participants. Four multimorbidity patterns were identified, including cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), gastrointestinal and hepatorenal multimorbidity (gallstone disease, chronic kidney disease, cirrhosis, peptic ulcer, and cancer), and mental and arthritis multimorbidity (neurasthenia, psychiatric disorder, and rheumatoid arthritis). During a median of 10.8 years of follow-up, 49,371 deaths occurred. Compared with participants without multimorbidity, cardiometabolic multimorbidity (hazard ratios [HR] = 2.20, 95% confidence intervals [CI]: 2.14 − 2.26) and respiratory multimorbidity (HR = 2.13, 95% CI:1.97 − 2.31) demonstrated relatively higher risks of mortality, followed by gastrointestinal and hepatorenal multimorbidity (HR = 1.33, 95% CI:1.22 − 1.46). The mortality risk increased by 36% (HR = 1.36, 95% CI: 1.35 − 1.37) with every additional disease.

Conclusion:

Cardiometabolic multimorbidity and respiratory multimorbidity posed the highest threat on mortality risk and deserved particular attention in Chinese adults.
Population genetic polymorphisms of pharmacogenes in Zimbabwe, a potential guide for the safe and efficacious use of medicines in people of African ancestry
Authors: Mbavha Bianza T. , Kanji Comfort R. , Stadler Nadina , Stingl Julia , Stanglmair Andrea , Scholl Catharina , Wekwete William , Masimirembwa Collen
Published: February 2022

Objective

Pharmacogenomics (PGx) is a clinically significant factor in the safe and efficacious use of medicines. While PGx knowledge is abundant for other populations, there are scarce PGx data on African populations and is little knowledge on drug–gene interactions for medicines used to treat diseases common in Africa. The aim of this study was to use a custom-designed open array to genotype clinically actionable variants in a Zimbabwean population. This study also identified some of the commonly used drugs in Zimbabwe and the associated genes involved in their metabolism.

Methods

A custom-designed open array that covers 120 genetic variants was used to genotype 522 black Zimbabwean healthy volunteers using TaqMan-based single nucleotide polymorphism genotyping. Data were also accessed from Essential Drugs’ List in Zimbabwe (EDLIZ), and the medicines were grouped into the associated biomarker groups based on their metabolism. We also estimated the national drug procurement levels for medicines that could benefit from PGx-guided use based on the data obtained from the national authorities in Zimbabwe.

Results

The results demonstrate the applicability of an open-array chip in simultaneously determining multiple genetic variants in an individual, thus significantly reducing cost and time to generate PGx data. There were significantly high frequencies of African-specific variants, such as the CYP2D6*17 and *29 variants and the CYP2B6*18 variant. The data obtained showed that the Zimbabwean population exhibits PGx variations in genes important for the safe and efficacious use of drugs approved by the EDLIZ and are procured at significantly large amounts annually. The study has established a cohort of genotyped healthy volunteers that can be accessed and used in the conduct of clinical pharmacogenetic studies for drugs entering a market of people of predominantly African ancestry.

Conclusion

Our study demonstrated the potential benefit of integrating PGx in Zimbabwe for the safe and efficacious use of drugs that are commonly used.
Obesity and abdominal obesity are risk factors for airway obstructive diseases in Korean women: nationwide population-based cohort study
Authors: Lee Chung-Woo , Kim HyunJin , Nam Myung Ji , Choi Yeon Joo , Han Kyungdo , Jung Jin-Hyung , Kim Do-Hoon , Park Joo-Hyun
Published: February 2022

Objective:

Existing studies show that women are more susceptible to chronic obstructive pulmonary disease (COPD) and asthma, and that obesity affects the risk of these airway obstructive diseases. We aimed to determine the effect of body mass index (BMI) and waist circumference (WC) on COPD and asthma development in premenopausal and postmenopausal women.

Methods:

This nationwide population-based cohort study included 1,644,635 women ages ≥30 years without diagnosis of COPD or asthma, who underwent national cancer screening in 2009. We classified them as premenopausal and postmenopausal women based on their menopause status at the time of cancer screening. Baseline BMI and WC were measured, and they were classified into five BMI groups (<18.5 kg/m2, 18.5-23 kg/m2, 23-25 kg/m2, 25-30 kg/m2, and ≥30 kg/m2) and WC groups (<60 cm, 65-75 cm, 75-85 cm, 85-95 cm, and ≥95 cm). The hazard ratios (HRs) for COPD and asthma were measured for each group.

Results:

Regardless of the menopausal status, the high BMI and WC groups had a significantly higher COPD and asthma incidence than that of the normal group, and the HRs increased further with increases in BMI and WC. However, the HR in the underweight group was significantly higher among the postmenopausal women. The HR for asthma in the obese group was significantly higher for both premenopausal and postmenopausal women. The HR for COPD was significantly higher in the group with a WC of ≥95 cm for both premenopausal and postmenopausal women, respectively; the HR for asthma was also significantly higher in this group.

Conclusions:

Obesity and abdominal obesity are risk factors for COPD and asthma in premenopausal and postmenopausal Korean women. Controlling weight and maintaining a healthy body shape can help prevent COPD and asthma in women.
Effectiveness of an individualized comprehensive rehabilitation program in women with chronic knee osteoarthritis: a randomized controlled trial
Authors: López Laura López , Benítez Paula Obeso , López Jesús Casilda , Martos Irene Cabrera , Torres Janet Rodríguez , Santiago María Granados , Valenza Marie-Carmen
Published: February 2022

Objective:

To evaluate the short- and medium-term effects of an 8-week individualized comprehensive rehabilitation program in women with chronic knee osteoarthritis as regards functionality, physical performance, and perceived health status.

Methods:

Women with chronic knee osteoarthritis were randomly assigned to the aquatic training group or to the individualized comprehensive rehabilitation (ICR) group. The main outcomes were functionality assessed with the Western Ontario and McMaster Universities Osteoarthritis Index, physical performance assessed with the Timed Up and Go test and the Stair Climbing Test, and perceived health status evaluated with the European Quality of Life- 5 Dimensions questionnaire. Participants were assessed after the treatment and at 3-month follow-up.

Results:

Forty participants were included in the study. After the treatment, there were no significant between- group differences. At 3-month follow-up, there were significant between-group differences in functionality (stiffness P = 0.049, function P = 0.005, and total subscores P = 0.048) and physical performance (Timed Up and Go P = 0.031 and Stair Climbing Test P = 0.046) in favor of the ICR group.

Conclusion:

An 8-week ICR program improved functionality, physical performance, and perceived health status compared with an aquatic training program in women with chronic knee osteoarthritis.
Rapid Deployment of Technology: Patient and Staff Empowerment at Houston Methodist
Authors: Schwartz Roberta
Published: February 2022

Digital innovations are arriving in healthcare at an increasing rate. Electronic medical records provided the foundation for this growth, and now thousands of technology companies are servicing every aspect of healthcare. Since 2018, Houston Methodist has been cultivating digital disruption, working to speed up the development of new initiatives. As our digital innovation has grown exponentially over the past few years, we have kept the patient at the center of all activities. We hold the philosophy that patient empowerment should be a process whereby patients understand their role and have access to knowledge that enables them to engage with their providers in a bidirectional relationship. Patient empowerment in the patient room, in care pathways, and in opioid reduction demonstrate the success of our approach with strongly positive outcomes. Importantly, the efforts are not only appreciated by our patients, but also widely embraced by our clinicians.
The Digital Transformation of a Metropolitan New York Health System
Authors: Mammen Adrin
Published: February 2022

Digital transformation strategies in healthcare are presenting unique ways to support patient acquisition and retention efforts. Montefiore Health System is on a multiyear, multipronged digital transformation journey with interventions centered on improving access to care.

Our patients can search for a provider, schedule a visit, get details about their visit, and check in through a welcoming digital front door. Asynchronous e-communication and video visits have also been implemented, and these added options are optimized by technologies including a new provider data management tool to support an enhanced provider directory, electronic health record system integration with online scheduling, telehealth/virtual care, and text message communications. Combined, these tactics support a positive patient experience. Happier patients are more likely to return for the care they need to improve their health and maintain wellness. In addition, digital solutions can alleviate administrative burdens, which can improve employee engagement and satisfaction.

While the lack of access to technology as a social determinant of health can present challenges in our diverse market, Montefiore has developed a respectful process to meet patients where they are in an era of consumer-driven healthcare. The process sets forth various approaches to bridge healthcare’s digital divide. The route is sequenced in a digital transformation road map to ensure that Montefiore remains competitive, provides value with operational efficiencies, and delivers the innovative care that is necessary in today’s healthcare landscape.
Asthma guidelines: comparison of the National Heart, Lung, and Blood Institute Expert Panel Report 4 with Global Initiative for Asthma 2021
Authors: Tan Laren D. , Alismail Abdullah , Ariue Barbara
Published: February 2022

Purpose of review

Asthma continues to be a prevalent respiratory disease that affects lives within the United States and worldwide. Clinical asthma guidelines based on scientific evidence on testing and therapeutic interventions are needed to control this disease better. To meet this need, the NAEPP (National Asthma Education and Prevention Program) and GINA (Global Initiative for Asthma) were formed to assist with best practice diagnosis and treatments for asthma. This paper reviews the subtle differences and similarities between the most recent recommendations put forth by NAEPP 2020 and GINA 2021, mainly examining the six selected topics, as well as methodology, guidance on emerging topics, and implementation.

Recent findings

In December 2020, the National Asthma Education and Prevention Program Coordinating Committee released their focused update on fraction of exhaled nitric oxide, indoor allergen mitigation, inhaled corticosteroids, long-acting muscarinic antagonists, allergen immunotherapy, and bronchial thermoplasty. The Global Initiative for Asthma comprehensive document is published annually as a framework for all nations. Therefore, it is timely to consider the National Asthma Education and Prevention Program Coordinating Committee 2020 in relation to the GINA 2021.

The comparison provides a better understanding of evidence-based recommendations for asthma. The NAEPP 2020 and GINA 2021 will equip providers with the knowledge to provide their patients with the best and most updated asthma care.
Potential options to expand the intestinal donor pool: a comprehensive review
Authors: Clarysse Mathias , Dubois Antoine , Vanuytsel Tim , Pirenne Jacques , Ceulemans Laurens J.
Published: February 2022

Purpose of review

Intestinal donation is currently restricted to ‘perfect’ donors, as the intestine is extremely vulnerable to ischemia. With generally deteriorating donor quality and increasing indications for intestinal transplantation (ITx), the potential to safely increase the donor pool should be evaluated.

Recent findings

Increasing awareness on intestinal donation (often forgotten) and cautiously broadening the strict donor criteria (increasing age, resuscitation time and ICU stay) could expand the potential donor pool. Donors after circulatory death (DCD) have so far not been considered for ITx, due to the particularly detrimental effect of warm ischemia on the intestine. However, normothermic regional perfusion might be a well tolerated strategy to render the use of DCD intestinal grafts feasible. Furthermore, machine perfusion is under continuous development and might improve preservation of the intestine and potentially offer a platform to modulate the intestinal graft. Lastly, living donation currently represents only a minority of all ITxs performed worldwide. Various studies and registry analysis show that it can be performed safely for the donor and successfully in the recipient.

Several potential strategies are available to expand the current intestinal donor pool. Most of them require further investigation or technical developments before they can be implemented in the clinical routine.
Health‐Related Quality of Life in Pediatric Acute Recurrent or Chronic Pancreatitis
Authors: Tham See Wan , Wang Fuchenchu , Gariepy Cheryl E. , Cress Gretchen A. , Abu‐El‐Haija Maisam A. , Bellin Melena D. , Ellery Kate M. , Fishman Douglas S. , Gonska Tanja , Heyman Melvin B. , Lin Tom K. , Maqbool Asim , McFerron Brian A. , Morinville Veronique D. , Nathan Jaimie D. , Ooi Chee Y. , Perito Emily R. , Schwarzenberg Sarah Jane , Sellers Zachary M. , Shah Uzma , Troendle David M. , Wilschanski Michael , Zheng Yuhua , Yuan Ying , Lowe Mark E. , Uc Aliye , Palermo Tonya M. ,   INternational Study Group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) and Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC)
Published: February 2022

Objectives:

Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health‐related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL.

Methods:

Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment.

Results:

The sample included 368 children (54.3% girls, mean age = 12.7years, standard deviation [SD] = 3.3); 65.2% had ARP and 34.8% with CP. Low physical HRQOL (M = 38.5, SD = 16.0) was demonstrated while psychosocial HRQOL (M = 49.5, SD = 10.2) was in the normative range. Multivariate regression analysis revealed that clinical levels of emotional and behavioral problems (B = –10.28, P < 0.001), episodic and constant abdominal pain (B = 04.66, P = 0.03; B = –13.25, P < 0.001) were associated with low physical HRQOL, after accounting for ARP/CP status, age, sex, exocrine, and endocrine disease (F [9, 271] = 8.34, P < 0.001). Borderline and clinical levels of emotional and behavioral problems (B = –10.18, P < 0.001; B = –15.98, P < 0.001), and constant pain (B = –4.46, P < 0.001) were associated with low psychosocial HRQOL (F [9, 271] = 17.18, P < 0.001).

Conclusions:

Findings highlight the importance of assessing HRQOL and treating pain and psychosocial problems in this vulnerable group of children.