bluuebunny/crossref_metadata_2025 huggingface dataset:
Active Surveillance and Contact Precautions for Preventing Methicillin-Resistant Staphylococcus aureus Healthcare-Associated Infections During the COVID-19 Pandemic
Authors: Evans Martin E , Simbartl Loretta A , McCauley Brian P , Flarida Linda K , Jones Makoto M , Harris Anthony D , Perencevich Eli N , Rubin Michael A , Hicks Natalie R , Kralovic Stephen M , Roselle Gary A
Published: June 2023

Background

Statistically significant decreases in methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated infections (HAIs) occurred in Veterans Affairs (VA) hospitals from 2007 to 2019 using a national policy of active surveillance (AS) for facility admissions and contact precautions for MRSA colonized (CPC) or infected (CPI) patients, but the impact of suspending these measures to free up laboratory resources for testing and conserve personal protective equipment for coronavirus disease 2019 (COVID-19) on MRSA HAI rates is not known.

Methods

From July 2020 to June 2022 all 123 acute care VA hospitals nationwide were given the rolling option to suspend (or re-initiate) any combination of AS, CPC, or CPI each month, and MRSA HAIs in intensive care units (ICUs) and non-ICUs were tracked.

Results

There were 917 591 admissions, 5 225 174 patient-days, and 568 MRSA HAIs. The MRSA HAI rate/1000 patient-days in ICUs was 0.20 (95% confidence interval [CI], .15–.26) for facilities practicing “AS + CPC + CPI” compared to 0.65 (95% CI, .41–.98; P < .001) for those not practicing any of these strategies, and in non-ICUs was 0.07 (95% CI, .05–.08) and 0.12 (95% CI, .08–.19; P = .01) for the respective policies. Accounting for monthly COVID-19 facility admissions using a negative binomial regression model did not change the relationships between facility policy and MRSA HAI rates. There was no significant difference in monthly facility urinary catheter-associated infection rates, a non-equivalent dependent variable, in the policy categories in either ICUs or non-ICUs.

Conclusions

Facility removal of MRSA prevention practices was associated with higher rates of MRSA HAIs in ICUs and non-ICUs.
Opportunities to improve the management of anemia in peritoneal dialysis patients: lessons from a national study in routine clinical practice
Authors: Portoles Jose , Serrano Salazar Maria Luisa , González Peña Olga , Gallego Domínguez Sandra , Vera Rivera Manel , Caro Espada Jara , Herreros García Alba , Munar Vila Maria Antonia , José Espigares Huete Maria , Sosa Barrios Haridian , Paraíso Vicente , Mariscal de Gante Loreto , Bajo Maria Auxiliadora , Mijaylova Antonia Gueorguieva , Pascual Pajares Elena , Areste Fosalba Nuria , Espinel Laura , Tornero Molina Fernando , Pizarro Sánchez Soledad , Ortega Díaz Mayra , Cases Aleix , Quiroga Borja
Published: June 2023

Background

Current guidelines establish the same hemoglobin (Hb) and iron biomarkers targets for hemodialysis (HD) and peritoneal dialysis (PD) in patients receiving erythropoiesis-stimulating agents (ESAs) even though patients having PD are usually younger, more active and less comorbid. Unfortunately, specific renal anemia [anemia in chronic kidney disease (aCKD)] trials or observational studies on PD are scanty. The aims of this study were to describe current aCKD management, goals and adherence to clinical guidelines, identifying opportunities for healthcare improvement in PD patients.

Methods

This was a retrospective, nationwide, multicentre study including patients from 19 PD units. The nephrologists collected baseline data, demographics, comorbidities and data related to anemia management (laboratory values, previously prescribed treatments and subsequent adjustments) from electronic medical records. The European adaptation of KDIGO guidelines was the reference for definitions, drug prescriptions and targets.

Results

A total of 343 patients (mean age 62.9 years, 61.2% male) were included; 72.9% were receiving ESAs and 33.2% iron therapy [20.7% intravenously (IV)]. Eighty-two patients were receiving ESA without iron therapy, despite 53 of them having an indication according to the European Renal Best Practice guidelines. After laboratory results, iron therapy was only started in 15% of patients. Among ESA-treated patients, 51.9% had an optimal control [hemoglobin (Hb) 10–12 g/dL] and 28.3% between 12–12.9 g/dL. Seventeen patients achieved Hb >13 g/dL, and 12 of them remained on ESA after overshooting. Only three patients had Hb <10 g/dL without ESAs. Seven patients (2%) met criteria for ESA resistance (epoetin dose >300 IU/kg/week). The highest tertile of erythropoietin resistance index (>6.3 UI/kg/week/g/dL) was associated with iron deficiency and low albumin corrected by renal replacement therapy vintage and hospital admissions in the previous 3 months.

Conclusion

Iron therapy continues to be underused (especially IV). Low albumin, iron deficiency and prior events explain most of the ESA hyporesponsiveness. Hb targets are titrated to/above the upper limits. Thus, several missed opportunities for adequate prescriptions and adherence to guidelines were identified.
Inferior vena cava ultrasound and other techniques for assessment of intravascular and extravascular volume: an update
Authors: Kaptein Elaine M , Kaptein Matthew J
Published: June 2023

Goals of volume management are to accurately assess intravascular and extravascular volume and predict response to volume administration, vasopressor support or volume removal.

Data are reviewed that support the following:

(i) Dynamic parameters reliably guide volume administration and may improve clinical outcomes compared with static parameters, but some are invasive or only validated with mechanical ventilation without spontaneous breathing.

(ii) Ultrasound visualization of inferior vena cava (IVC) diameter variations with respiration reliably assesses intravascular volume and predicts volume responsiveness.

(iii) Although physiology of IVC respiratory variations differs with mechanical ventilation and spontaneous breathing, the IVC collapsibility index (CI) and distensibility index are interconvertible.

(iv) Prediction of volume responsiveness by IVC CI is comparable for mechanical ventilation and spontaneous breathing patients.

(v) Respiratory variations of subclavian/proximal axillary and internal jugular veins by ultrasound are alternative sites, with comparable reliability.

(vi) Data support clinical applicability of IVC CI to predict hypotension with anesthesia, guide ultrafiltration goals, predict dry weight, predict intra-dialytic hypotension and assess acute decompensated heart failure.

(vii) IVC ultrasound may complement ultrasound of heart and lungs, and abdominal organs for venous congestion, for assessing and managing volume overload and deresuscitation, renal failure and shock.

(viii) IVC ultrasound has limitations including inadequate visualization.

Ultrasound data should always be interpreted in clinical context. Additional studies are required to further assess and validate the role of bedside ultrasonography in clinical care.
Pathogenesis and management of abdominal aortic aneurysm
Authors: Golledge Jonathan , Thanigaimani Shivshankar , Powell Janet T , Tsao Phil S
Published: June 2023

Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in men) are monitored by imaging and large asymptomatic, symptomatic, and ruptured AAAs are considered for surgical repair. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. This review outlines research on AAA pathogenesis and therapies to limit AAA growth. Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. Mendelian randomization analyses suggest that treatments to reduce low-density lipoprotein cholesterol such as proprotein convertase subtilisin/kexin type 9 inhibitors and smoking reduction or cessation are also treatment targets. Thirteen placebo-controlled randomized trials have tested whether a range of antibiotics, blood pressure–lowering drugs, a mast cell stabilizer, an anti-platelet drug, or fenofibrate slow AAA growth. None of these trials have shown convincing evidence of drug efficacy and have been limited by small sample sizes, limited drug adherence, poor participant retention, and over-optimistic AAA growth reduction targets. Data from some large observational cohorts suggest that blood pressure reduction, particularly by angiotensin-converting enzyme inhibitors, could limit aneurysm rupture, but this has not been evaluated in randomized trials. Some observational studies suggest metformin may limit AAA growth, and this is currently being tested in randomized trials. In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.
Mechanisms of fever-induced QT prolongation and torsades de pointes in patients with KCNH2 mutation
Authors: Usuda Keisuke , Hayashi Kenshi , Nakajima Tadashi , Kurata Yasutaka , Cui Shihe , Kusayama Takashi , Tsuda Toyonobu , Tada Hayato , Kato Takeshi , Sakata Kenji , Usui Soichiro , Fujino Noboru , Tanaka Yoshihiro , Kaneko Yoshiaki , Kurabayashi Masahiko , Tange Shoichi , Saito Takekatsu , Ohta Kunio , Yamagishi Masakazu , Takamura Masayuki
Published: June 2023

Aims

Patients with particular mutations of type-2 long QT syndrome (LQT2) are at an increased risk for malignant arrhythmia during fever. This study aimed to determine the mechanism by which KCNH2 mutations cause fever-induced QT prolongation and torsades de pointes (TdP).

Methods and results

We evaluated three KCNH2 mutations, G584S, D609G, and T613M, in the Kv11.1 S5-pore region, identified in patients with marked QT prolongation and TdP during fever. We also evaluated KCNH2 M124T and R269W, which are not associated with fever-induced QT prolongation. We characterized the temperature-dependent changes in the electrophysiological properties of the mutant Kv11.1 channels by patch-clamp recording and computer simulation. The average tail current densities (TCDs) at 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller and less increased with rising temperature from 35°C to 40°C than those for WT, M124T, and R269W. The ratios of the TCDs at 40°C to 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller than for WT, M124T, and R269W. The voltage dependence of the steady-state inactivation curve for WT, M124T, and R269W showed a significant positive shift with increasing temperature; however, that for G584S, WT+D609G, and WT+T613M showed no significant change. Computer simulation demonstrated that G584S, WT+D609G, and WT+T613M caused prolonged action potential durations and early afterdepolarization formation at 40°C.

Conclusion

These findings indicate that KCNH2 G584S, D609G, and T613M in the S5-pore region reduce the temperature-dependent increase in TCDs through an enhanced inactivation, resulting in QT prolongation and TdP at a febrile state in patients with LQT2.
Trans-Acting Genotypes Associated with mRNA Expression Affect Metabolic and Thermal Tolerance Traits
Authors: Drown Melissa K , Oleksiak Marjorie F , Crawford Douglas L
Published: June 2023

Evolutionary processes driving physiological trait variation depend on the underlying genomic mechanisms. Evolution of these mechanisms depends on the genetic complexity (involving many genes) and how gene expression impacting the traits is converted to phenotype. Yet, genomic mechanisms that impact physiological traits are diverse and context dependent (e.g., vary by environment and tissues), making them difficult to discern. We examine the relationships between genotype, mRNA expression, and physiological traits to discern the genetic complexity and whether the gene expression affecting the physiological traits is primarily cis- or trans-acting. We use low-coverage whole genome sequencing and heart- or brain-specific mRNA expression to identify polymorphisms directly associated with physiological traits and expressed quantitative trait loci (eQTL) indirectly associated with variation in six temperature specific physiological traits (standard metabolic rate, thermal tolerance, and four substrate specific cardiac metabolic rates). Focusing on a select set of mRNAs belonging to co-expression modules that explain up to 82% of temperature specific traits, we identified hundreds of significant eQTL for mRNA whose expression affects physiological traits. Surprisingly, most eQTL (97.4% for heart and 96.7% for brain) were trans-acting. This could be due to higher effect size of trans- versus cis-acting eQTL for mRNAs that are central to co-expression modules. That is, we may have enhanced the identification of trans-acting factors by looking for single nucleotide polymorphisms associated with mRNAs in co-expression modules that broadly influence gene expression patterns. Overall, these data indicate that the genomic mechanism driving physiological variation across environments is driven by trans-acting heart- or brain-specific mRNA expression.
Examining Utilization of Formal Supports and Related Impacts on Overall Well-Being Among East Asian American Family Caregivers of Persons With Dementia: A Mixed-Methods Study
Authors: Lee Kathy , Cassidy Jessica , Lee Jihui , Seo Chang Hyun , Kunz Lomelin Alan , Shin Hye-Won , Grill Joshua D
Published: June 2023

Background and Objectives

Although East Asian American family caregivers are known to underutilize formal support services, there is a lack of evidence regarding the associations of formal service utilization with caregivers’ well-being. This study examined the prevalence of different types of home-and community-based formal service utilization among Korean and Chinese American family caregivers of persons with dementia and how utilization of such services was associated with their well-being. We also explored their overall experience in accessing and utilizing formal dementia support services and programs.

Research Design and Methods

We employed a convergent mixed-methods study design. In a convenience sampling method, we recruited 62 family caregivers. Logistic regression and thematic analysis were utilized to analyze data.

Results

The results showed in-home services were mostly utilized among family caregivers of these ethnic groups. Out of 9 different support services, those who utilized nutrition programs and case management were more likely to report higher overall well-being. Four themes were developed: (1) awareness of formal support services but uncertainty on how to access them, (2) language barriers imposing additional challenges in accessing formal support services, (3) traveling to access culturally appropriate services, and (4) desire for culturally tailored medical and long-term care services.

Discussion and Implications

Findings from this study suggest the importance of case management services to overcome barriers to accessing and utilizing a wide range of formal support services and provision of culturally appropriate food in formal support services to increase East Asian American family caregivers’ utilization of long-term care services.
Grace Period Harmonization in the Open Innovation Era
Authors: Takenaka Toshiko
Published: June 2023

This article urges European companies to discard their prejudices and work with their patent offices to adopt a grace period in the European Patent Convention (‘EPC’) in exchange for the United States’ reconciliation of the definition of the prior art, harmonizing the differences remaining after the America Invents Act (AIA). The negative view that European companies have taken of a grace period is contrary to the experience in Japan, where an unrestricted grace period helped large companies engage in open innovation and increase their use. Empirical studies have substantiated the negative impacts of the lack of a grace period on European SMEs and Universities. After highlighting the differences in the prior art under AIA and EPC, this article will conclude with a proposal for a 12-month, U.S.-style grace period to harmonize the patent systems in Paris Union member states. The adoption of this proposed grace period would result in a win-win outcome for both the United States and European countries.
Could Cesarean Delivery Help Prevent Mother-to-Child Transmission of Human T-Lymphotropic Virus Type 1?
Authors: Prates Gabriela , Paiva Arthur , Haziot Michel E , Fonseca Luiz Augusto M , Smid Jerusa , Marcusso Rosa Maria do N , Assone Tatiane , de Oliveira Augusto C P , Casseb Jorge
Published: June 2023

Background

Mother-to-child transmission (MTCT) of human T-lymphotropic virus type 1 (HTLV-1) is an important route of transmission that can cause lifelong infection. There is high morbidity and mortality due to adult T-cell leukemia/lymphoma, HTLV-1–associated myelopathy (HAM), and other inflammatory disorders. These conditions develop in nearly 10% of people with HTLV-1 infection, with a higher risk if infection occurs early in life. Identification of risk factors can inform targeted measures to reduce HTLV-1 MTCT. This study aimed to investigate the potential of cesarean delivery to prevent HTLV-1 MTCT.

Methods

We performed a review of the cases of women and their offspring under regular follow-up at the HTLV-1 outpatient clinic at the Institute of Infectious Diseases Emilio Ribas.

Results

A total of 177 HTLV-1–infected women and 369 adult offspring were investigated. Overall, 15% of the children were positive for HTLV-1 and 85% were negative. Regarding vertical transmission, we found that a breastfeeding duration of >6 months was associated with MTCT. Moreover, maternal proviral load was not associated with transmission, but high educational level and cesarean delivery were identified as protective factors.

Conclusions

HTLV-1 MTCT was associated with mother's age at delivery of >25 years, low educational level, prolonged breastfeeding, and vaginal delivery.
Ebola Virus Tropism in Ex Vivo Cynomolgus Macaque Ocular Tissues
Authors: Matson M Jeremiah , Bushmaker Trent , Scott Dana P , Rosenke Rebecca , Saturday Greg , Chertow Daniel S , Munster Vincent J
Published: June 2023

Ocular complications of Ebola virus disease are well-documented and long-term sequelae in survivors are common and lead to considerable morbidity. However, little is currently known regarding EBOV's tropism and replication kinetics within the eye. To date, limited studies have utilized in vitro infections of ocular cell lines and analyses of archived pathology samples to investigate these issues. Here, we employed ex vivo cultures of cynomolgus macaque eyes to determine the tropism of EBOV in 7 different ocular tissues: cornea, anterior sclera with bulbar conjunctiva, ciliary body, iris, lens, neural retina, and retina pigment epithelium. We report that, except for neural retina, all tissues supported EBOV replication. Retina pigment epithelium produced the fastest growth and highest viral RNA loads, although the differences were not statistically significant. Immunohistochemical staining confirmed and further characterized infection. This study demonstrates that EBOV has a broad tropism within the eye.
Outcomes of a multifaceted intervention to prevent eclampsia and eclampsia-related deaths in Nigerian referral facilities
Authors: Okonofua Friday , Ekezue Bola F , Ntoimo Lorretta Favour , Ohenhen Victor , Agholor Kingsley , Imongan Wilson , Ogu Rosemary , Galadanci Hadiza
Published: June 2023

Background

Eclampsia causes maternal mortality in Nigeria. This study presents the effectiveness of multifaceted interventions that addressed institutional barriers in reducing the incidence and case fatality rates associated with eclampsia.

Methods

The design was quasi-experimental and the activities implemented at intervention hospitals included a new strategic plan, retraining health providers on eclampsia management protocols, clinical reviews of delivery care and educating pregnant women and their partners. Prospective data were collected monthly on eclampsia and related indicators from study sites over 2 y. The results were analysed by univariate, bivariate and multivariable logistic regression.

Results

The results show a higher eclampsia rate (5.88% vs 2.45%) and a lower use of partograph and antenatal care (ANC; 17.99% vs 23.42%) in control compared with intervention hospitals, but similar case fatality rates of <1%. Overall, adjusted analysis shows a 63% decrease in the odds of eclampsia at intervention compared with control hospitals. Factors associated with eclampsia were ANC, referral for care from other facilities and older maternal age.

Conclusion

We conclude that multifaceted interventions that address challenges associated with managing pre-eclampsia and eclampsia in health facilities can reduce eclampsia occurrence in referral facilities in Nigeria and potential eclampsia death in resource-poor African countries.
Survey of clinical informatics fellows graduating 2016–2024: experiences before and during fellowship
Authors: Kim Ellen , Van Cain Melissa , Hron Jonathan
Published: June 2023

Objective

To describe experiences and activities of Clinical Informatics (CI) fellows since the first fellowships were accredited in 2014.

Materials and Methods

We performed a voluntary and anonymous survey of 394 alumni and current clinical informatics fellows from the graduating classes of 2016–2024 in the summer of 2022.

Results

We received 198 responses; 2% declined to participate. Most were male (62%), White (39%), 31–40 years old (72%), from primary care specialties (54%) and nonprocedural specialties (95%), and without prior informatics experience or any careers before medicine. Most fellows (87–94%) participated significantly in operations, research, coursework, quality improvement, and clinical care activities during fellowship.

Discussion

Women, underrepresented racial and ethnic minorities, and procedural physicians were underrepresented. Many incoming CI fellows did not have an informatics background. During CI fellowship, trainees earned Master’s degrees and certificates, were exposed to many different types of CI activities, and were able to spend most of their time pursuing projects that supported their personal career goals.

Conclusion

These findings represent the most comprehensive report to date of CI fellows and alumni. Physicians without prior informatics experience who are interested in CI should be encouraged to apply because CI fellowship provides a strong foundation of informatics knowledge while supporting fellows’ personal career goals. There remains a lack of women and underrepresented minorities in CI fellowship programs; efforts to expand the pipeline are needed.
The Effect of Pursuing Self-Regulatory Goals on Variety Seeking
Authors: Rafieian Hoori , Huang Yanliu , Kahn Barbara E
Published: June 2023

Pursuing a self-regulatory goal, such as weight loss, motivates consumers to forego pleasure seeking, typically by selecting virtue over vice. We propose that in the absence of virtuous options, consumers with a self-regulatory goal will instead choose less variety in choice sets of exclusively vice options because the extra pleasure that variety affords seems incompatible with the goal. We find converging evidence for the decrease in variety seeking in vice categories across five studies (and three supplementary studies in the web appendix, N = 6,066), using both scenario-based and actual consumption contexts. We also demonstrate the underlying process: consumers are motivated to curtail pleasure seeking when pursuing a weight-loss goal and that leads them to choose less variety in vice categories when there is no virtue alternative available.
The impact of online medication reviews and educational workshops on deprescribing during the COVID-19 pandemic: a controlled before-after study
Authors: Al-Sakran Lina , Carney Gregory , Maclure Malcolm , Fisher Anat , Perry Thomas , Dormuth Colin
Published: June 2023

Objectives

The South Peace Polypharmacy Reduction Project is a quality improvement project in three communities in rural Canada that aimed to reduce polypharmacy and inappropriate prescribing practices in older adults. This study aims to evaluate the impact of a multifaceted intervention consisting of online team-based medication reviews and educational workshops on the number of chronic medications.

Methods

A controlled before-after design was used to compare if a decrease in the number of chronic medications was associated with the intervention comprising of online team-based medication reviews and educational workshops, compared with two matched control groups that received either a standard medication review or no medication review. Logistic regression models fit with generalized estimated equations were used to identify the impact of the interventions on decreasing the number of chronic medications.

Key findings

Following a medication review, the percentage of individuals that had deprescribed at least one medication was highest in the intervention group (52%), followed by the medication review controls at 45%, and 36% in non-medication review controls. Individuals in the intervention group were 20% more likely to have at least one medication deprescribed than individuals in the medication review control group (adjusted odds ratio: 1.20; 95% CI: 1.03 to 1.39), whereas they were 42% more likely to deprescribe at least one medication compared with non-medication review controls (adjusted odds ratio: 1.42; 95% CI: 1.25 to 1.61).

Conclusions

Online team-based medication reviews had a significant impact on decreasing the number of chronic medications in older adults. Furthermore, providing healthcare providers with education can complement the role of other healthcare interventions.
NGC 2022, a case study of a multiple-shell planetary nebula
Authors: Montoro-Molina B , Guerrero M A , Santamaría E , Toalá J A , Chu Y-H , Ramos-Larios G , Infante-Sainz R , Akhlaghi M , Eskandarlou S , López-Sanjuan C
Published: June 2023

We present a detailed study of the physical properties, history of mass loss, and chemical abundances of the planetary nebula NGC 2022. New imaging observations obtained with the OAJ/JAST80 and NOT/ALFOSC confirm the presence of a faint ∼88 arcsec halo surrounding a double-layered elliptical structure that consists of a bright 21.4 × 16.7 arcsec inner shell and a 32 arcsec diameter envelope. The long-slit high-dispersion echelle observations obtained with MES on the OAN-SPM 2.1-m telescope can be well described by a shape model with expansion velocities of 43 ± 3 and 34 ± 3 km s−1 along the major and minor axes of the elliptical inner shell, respectively. In addition, a deep long-slit high-dispersion echelle observation made with the KPNO 4-m telescope detected line-splitting in the faint halo, revealing an expansion velocity of 15.5 ± 2 km s−1. We have also used new intermediate-dispersion optical spectra with the NOT, complemented with IUE data, to study the chemical abundances of each shell. The abundances of the three shells are typical of a Type II in the Peimbert classification of PNe and do not exhibit any notable anomalies. Finally, we estimate the total mass of NGC 2022 to be ≈0.9 M⊙, which consists of 0.64 M⊙ from the CSPN and 0.1, 0.11, and 0.1 × $f_{\mathrm{halo}}^{1/2}$ M⊙ from the ionized inner shell, outer shell, and halo, respectively.
On the degree of dynamical packing in the Kepler multiplanet systems
Authors: Obertas Alysa , Tamayo Daniel , Murray Norm
Published: June 2023

Current planet formation theories rely on initially compact orbital configurations undergoing a (possibly extended) phase of giant impacts following the dispersal of the dissipative protoplanetary disc. The orbital architectures of observed mature exoplanet systems have likely been strongly sculpted by chaotic dynamics, instabilities, and giant impacts. One possible signature of systems continually reshaped by instabilities and mergers is their dynamical packing. Early Kepler data showed that many multiplanet systems are maximally packed – placing an additional planet between an observed pair would make the system unstable. However, this result relied on placing the inserted planet in the most optimistic configuration for stability (e.g. circular orbits). While this would be appropriate in an ordered and dissipative picture of planet formation (i.e. planets dampen into their most stable configurations), we argue that this best-case scenario for stability is rarely realized due to the strongly chaotic nature of planet formation. Consequently, the degree of dynamical packing in multiplanet systems under a realistic formation model is likely significantly higher than previously realized. We examine the full Kepler multiplanet sample through this new lens, showing that $\sim 60{{-}}95~{{\ \rm per\ cent}}$ of Kepler multiplanet systems are strongly packed and that dynamical packing increases with multiplicity. This may be a signature of dynamical sculpting or of undetected planets, showing that dynamical packing is an important metric that can be incorporated into planet formation modelling or when searching for unseen planets.
Into the High to Ultrahigh Temperature Melting of Earth’s Crust: Investigation of Melt and Fluid Inclusions within Mg-Rich Metapelitic Granulites from the Mather Peninsula, East Antarctica
Authors: Liu Zhao , Carvalho Bruna B , Li Wancai , Tong Laixi , Bartoli Omar , Chen Longyao , Yan Qinghe , Wu Haobo
Published: June 2023

Precise constraints on the compositions of melts generated by anatexis under ultrahigh temperature (UHT) conditions are critical for understanding processes of partial melting and differentiation of the Earth’s crust. Here we reveal geochemical and physical signatures of anatectic melts preserved as nanogranitoids (i.e. crystalized melt inclusions) within sapphirine-bearing UHT metapelitic granulites from the Mather Peninsula, East Antarctica. Their coexistence with high−Al orthopyroxene as inclusions in garnets strongly suggests that the investigated melts were at least partially UHT in origin. The nanogranitoids are enriched in SiO2 (69.9–75.6 wt.%), strongly peraluminous (ASI values = 1.2–1.6) and potassic to ultrapotassic (Na2O + K2O = 7.1–9.5 wt.%, K/Na = 2.2–9.3). When compared to the granulitic restite, the melts are enriched in Li, Cs, Rb, Ta, Sm, Nd, Zr, U and Pb, and depleted in Ce, Th, Ba, Sr and Nb. Their geochemical characteristics are consistent with biotite−dehydration melting in the absence of plagioclase. Our calculation results indicate that these hot crustal melts have low densities of 2.47 ± 0.07 g/cm3, low viscosities of 104.9 ± 1.2 Pa·s and high heat production values of ∼2.8 μW/m3. Therefore, such melts are mobile and susceptible to be extracted from the source, and consequently their flow and removal from the deep crust may greatly affect the chemical and thermal structure of the continental crust.

Secondary C − O − H fluid inclusions within garnet and orthopyroxene have also been detected. These inclusions contain magnesite, pyrophyllite, corundum, with or without residual CO2. The minerals within the fluid inclusions are interpreted as stepdaughter minerals, which were produced by the reaction of the fluid with its host. The metamorphic timing of the investigated rocks is still a matter of debate. Zircon U–Pb dating results obtained in this study suggest that the metapelitic granulites may have undergone two separated thermal events at ∼1000 and ∼530 Ma, respectively. The presence of fluid inclusions indicates that fluid infiltration and Pan–African reworking may have played an important role in obscuring chronological information of the early thermal scenario in poly-metamorphic terranes.
Moisture stress limits radial mixing of non-structural carbohydrates in sapwood of trembling aspen
Authors: Peltier Drew M P , Nguyen Phiyen , Ebert Chris , Koch George W , Schuur Edward A G , Ogle Kiona
Published: June 2023

Dynamics in non-structural carbohydrate (NSC) pools may underlie observed drought legacies in tree growth. We assessed how aridity influences the dynamics of different-aged NSC pools in tree sapwood at two sites with differing climate conditions (‘wet’ vs ‘dry’), which also experienced widespread regional drought 5 years earlier. We used an incubation method to measure the radiocarbon (Δ14C) in CO2 respired from Populus tremuloides Michx. (aspen) tree rings to evaluate NSC storage and mixing patterns, coupled with measurements of NSC (soluble sugars and starch) concentrations and respired δ13C-CO2. At a wet site, CO2 respired from rings formed during 1962–67 was only ~11 years old, suggesting deep sapwood mixing of NSCs as starch. At a dry site, the total NSC was about one-third of wet-site totals, maximum ages in deep rings were lower and ages more rapidly increased in shallow rings and then plateaued. These results suggest historically shallower mixing and/or relatively higher consumption of NSCs under dry conditions. Both sites, however, had similar aged NSC (<1 year) in the most recent six rings, indicative of deep radial mixing following relatively wet conditions during the sampling year. We suggest that the significant differences in NSC mixing among sites are driven by moisture stress, where aridity reduces NSC reserves and restricts the depth of radial mixing. However, dynamic climate conditions in the south-western USA resulted in more complex radial patterns of sapwood NSC age than previously described. We suggest a novel conceptual framework to understand how moisture variability might influence the dynamics of NSC mixing in the sapwood.
Morphological, ontogenetic, and molecular investigations of freshwater hypotrich ciliates from China revealed a new genus Heterodeviata gen. nov. (Protista: Ciliophora), and a novel limnetic population of Deviata multilineae
Authors: Song Wenya , Dong Jingyi , Lu Xiaoteng , Al-Farraj Saleh A , Song Weibo , Hines Hunter N , Luo Xiaotian
Published: June 2023

Hypotrichs are among the most complex and highly differentiated ciliate lineages, which are distributed in diverse habitats. Members of the family Deviatidae Foissner, 2016 are commonly found in freshwater or low-salinity habitats, as well as soils. During a study of freshwater wetland diversity in China, a novel deviatid ciliate Heterodeviata sinica gen. nov. et sp. nov. and a distinct population of Deviata multilineae Zhang et al., 2022 were investigated based on morphology, morphogenesis, and 18S rRNA gene sequences. The new genus Heterodeviata gen. nov. can be characterized by having two or more left and right marginal rows each, one frontoventral cirral row, the presence of caudal cirri, and two dorsal kineties, one of them being a dorsomarginal kinety. Phylogenetic analyses reveal that Heterodeviata is nested in a well-supported clade with Deviata Eigner, 1995, Perisincirra Jankowski, 1978 and Pseudosincirra Gao et al., 2021, which suggests that the family Deviatidae is monophyletic. The close relationship among the Deviatidae genera were supported after extensive morphological and morphogenetic investigations, as well as molecular phylogeny presented here.
Genome-Wide Association Mapping and Genomic Prediction of Fusarium Wilt Race 2 Resistance in the USDA Citrullus amarus Collection
Authors: Ganaparthi Venkata Rao , Rennberger Gabriel , Wechter Patrick , Levi Amnon , Branham Sandra E.
Published: June 2023

Fusarium wilt caused by Fusarium oxysporum f. sp. niveum (Fon) race 2 is a serious disease in watermelon and can reduce yields by 80%. Genome-wide association studies (GWAS) are a valuable tool in dissecting the genetic basis of traits. Citrullus amarus accessions (n = 120) from the USDA germplasm collection were genotyped with whole-genome resequencing, resulting in 2,126,759 single nucleotide polymorphic (SNP) markers that were utilized for GWAS. Three models were used for GWAS with the R package GAPIT. Mixed linear model (MLM) analysis did not identify any significant marker associations. FarmCPU identified four quantitative trait nucleotides (QTN) on three different chromosomes (i.e., chromosomes 1, 5, and 9), and Bayesian-information and linkage-disequilibrium iteratively nested keyway (BLINK) identified one QTN on chromosome 10 as significantly associated with Fon race 2 resistance. FarmCPU identified four QTN that explained 60% of Fon race 2 resistance, and the single QTN from BLINK explained 27%. Relevant candidate genes were found within the linkage disequilibrium (LD) blocks of these significant SNPs, including genes encoding aquaporins, expansins, 2S albumins, and glutathione S-transferases which have been shown to be involved in imparting resistance to Fusarium spp. Genomic predictions (GP) for Fon race 2 resistance using all 2,126,759 SNPs resulted in a mean prediction accuracy of 0.08 with five-fold cross-validation employing genomic best linear unbiased prediction (gBLUP) or ridge-regression best linear unbiased prediction (rrBLUP). Mean prediction accuracy with gBLUP leave-one-out cross-validation was 0.48. Thus, along with identifying genomic regions associated with Fon race 2 resistance among the accessions, this study observed prediction accuracies that were strongly influenced by population size.
Dickkopf‐1 promotes vascular smooth muscle cell foam cell formation and atherosclerosis development through CYP4A11/SREBP2/ABCA1
Authors: Li Xiao , Zheng Tengfei , Zhang Yu , Zhao Yachao , Liu Fengming , Dai Shen , Liu Xiaolin , Zhang Mei
Published: June 2023

Vascular smooth muscle cells (VSMCs) are considered to be a crucial source of foam cells in atherosclerosis due to their low expression level of cholesterol exporter ATP‐binding cassette transporter A1 (ABCA1) intrinsically. While the definite regulatory mechanisms are complicated and have not yet been fully elucidated, we previously reported that Dickkopf‐1 (DKK1) mediates endothelial cell (EC) dysfunction, thereby aggravating atherosclerosis. However, the role of smooth muscle cell (SMC) DKK1 in atherosclerosis and foam cell formation remains unknown. In this study, we established SMC‐specific DKK1‐knockout (DKK1SMKO) mice by crossbreeding DKK1flox/flox mice with TAGLN‐Cre mice. Then, DKK1SMKO mice were crossed with APOE−/− mice to generate DKK1SMKO/APOE−/− mice, which exhibited milder atherosclerotic burden and fewer SMC foam cells. In vitro loss‐ and gain‐of‐function studies of DKK1 in primary human aortic smooth muscle cells (HASMCs) have proven that DKK1 prevented oxidized lipid‐induced ABCA1 upregulation and cholesterol efflux and promoted SMC foam cell formation. Mechanistically, RNA‐sequencing (RNA‐seq) analysis of HASMCs as well as chromatin immunoprecipitation (ChIP) experiments showed that DKK1 mediates the binding of transcription factor CCAAT/enhancer‐binding protein delta (C/EBPδ) to the promoter of cytochrome P450 epoxygenase 4A11 (CYP4A11) to regulate its expression. In addition, CYP4A11 as well as its metabolite 20‐HETE‐promoted activation of transcription factor sterol regulatory element‐binding protein 2 (SREBP2) mediated the DKK1 regulation of ABCA1 in SMC. Furthermore, HET0016, the antagonist of CYP4A11, has also shown an alleviating effect on atherosclerosis. In conclusion, our results demonstrate that DKK1 promotes SMC foam cell formation during atherosclerosis via a reduction in CYP4A11‐20‐HETE/SREBP2‐mediated ABCA1 expression.
The Impact of Multidisciplinary Approaches to Social Functioning on Surgical Outcomes Following Surgery for Cervical Myelopathy
Authors: Tamai Koji , Terai Hidetomi , Watanabe Shingo , Tashiro Yoji , Omine Toshimitsu , Katsuda Hiroshi , Shimada Nagakazu , Kobayashi Yuto , Nakamura Hiroaki
Published: June 2023

Study Design.

Prospective cohort study

Objective.

To identify the effects of multidisciplinary approaches (MAs) to improve social functioning (SF) on 1-year surgical outcomes in patients with cervical myelopathy

Summary of Background Data.

Despite significant improvement in cervical myelopathy, a patient’s quality of life (QOL) sometimes does not improve postoperatively. A previous study revealed that SF, rather than myelopathy severity, correlated with QOL improvement after decompression surgery for cervical myelopathy.

Methods.

This study compared two prospective cohorts in Japan. Patients who underwent cervical laminoplasty for cervical myelopathy from 2018 to 2020 were enrolled in the control cohort. Patients who underwent the same surgery with the same indications between 2020 and 2021 were enrolled in the MA cohort. Patients in the control cohort were treated with a standard care protocol and those in the MA cohort were treated with a multidisciplinary protocol that focused on SF improvement. The changes in the total JOA score and in the domains of the JOA scores (upper limb function, lower limb function, upper limb sensory, and lower limb sensory) from preoperatively to 1 year postoperatively were compared between the control and MA cohorts using a mixed-effect model.

Results.

The control and MA cohorts comprised 140 and 31 patients, respectively. The improvement in the Japanese Orthopaedic Association (JOA) score was significantly better in the MA cohort than in the control cohort (P=0.040). In analyses of each JOA score domain, the improvement of upper limb function was significantly better in the MA cohort than in the control cohort (P=0.033). Similarly, the MA cohort demonstrated significantly higher patient-reported outcome for upper extremity function than the control cohort (P<0.001). Additionally, the self-care domain of QOL score at 1 year postoperatively was significantly higher in the MA cohort than in the control cohort (P=0.047).

Conclusion.

MAs to improve/rebuild a patient’s SF were effective in improving cervical myelopathy and self-care domain of QOL. This study is the first to demonstrate the effectiveness of a postoperative MAs in patients with cervical myelopathy.

Level of Evidence.

III
Ginsenoside Rg1 improves anti-tumor efficacy of adoptive cell therapy by enhancing T cell effector functions
Authors: Liu Yue , An Lingna , Yang Chengfei , Wang Xiaoqi , Huang Ruihao , Zhang Xi
Published: June 2023

Adoptive cell therapy (ACT) has emerged with remarkable efficacies for tumor immunotherapy. Chimeric antigen receptor (CAR) T cell therapy, as one of most promising ACTs, has achieved prominent effects in treating malignant hematological tumors. However, the insufficient killing activity and limited persistence of T cells in the immunosuppressive tumor microenvironment limit the further application of ACTs for cancer patients. Many studies have focused on improving cytotoxicity and persistence of T cells to achieve improved therapeutic effects. In this study, we explored the potential function in ACT of ginsenoside Rg1, the main pharmacologically active component of ginseng. We introduced Rg1 during the in vitro activation and expansion phase of T cells, and found that Rg1 treatment upregulated two T cell activation markers, CD69 and CD25, while promoting T cell differentiation towards a mature state. Transcriptome sequencing revealed that Rg1 influenced T cell metabolic reprogramming by strengthening mitochondrial biosynthesis. When co-cultured with tumor cells, Rg1-treated T cells showed stronger cytotoxicity than untreated cells. Moreover, adding Rg1 to the culture endowed CAR-T cells with enhanced anti-tumor efficacy. This study suggests that ginsenoside Rg1 provides a potential approach for improving the anti-tumor efficacy of ACT by enhancing T cell effector functions.
Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer
Authors: Qiu Shi , Qiu Yaqi , Deng Linghui , Nie Ling , Ge Liming , Zheng Xiaonan , Jin Di , Jin Kun , Zhou Xianghong , Su Xingyang , Cai Boyu , Li Jiakun , Tu Xiang , Gong Lina , Liu Liangren , Liu Zhenhua , Bao Yige , Ai Jianzhong , Lin Tianhai , Yang Lu , Wei Qiang
Published: June 2023

Background:

Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.

Methods:

The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.

Results:

Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.

Conclusions:

The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
Evolving best practices in the surgical management of endometriosis – examining the evidence and expert opinion
Authors: Jorgensen Elisa , Fitzgerald Alison , Clark Nisse
Published: June 2023

Purpose of review

Endometriosis is a common and often debilitating condition, with multiple theories of pathogenesis. Despite the prevalence of endometriosis, the optimal surgical management remains unclear.

Recent findings

Laparoscopy is the gold standard for the diagnosis of endometriosis, with biopsy confirmation more accurate than visual diagnosis alone. It is not clear from the existing data whether excision of endometriosis is superior to ablation. Improvement in pain has been documented following peritonectomy, however, controlled trials are lacking. It is not clear whether concomitant hysterectomy improves pain associated with endometriosis, although hysterectomy may reduce reoperation rate. Bilateral oophorectomy performed for the treatment of endometriosis may not be curative without simultaneous excision of all visible lesions, and the risks of surgical menopause should be considered. The rate of appendiceal endometriosis is higher than previously suspected, and may not correlate with intraoperative visual findings, suggesting appendectomy should be considered during surgical treatment of endometriosis.

Despite the prevalence of endometriosis, there is a paucity of data to guide optimal surgical management. More high-quality studies are needed.