bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability of closedness of semi-algebraic sets under continuous semi-algebraic mappings
Authors: Đinh Sĩ , Jelonek Zbigniew , Phạm Tiến
Published: June 2022

Given a closed semi-algebraic set

X
⊂

R

n

X \subset \mathbb {R}^n

and a continuous semi-algebraic mapping

G
:
X
→

R

m

G \colon X \to \mathbb {R}^m

, it will be shown that there exists an open dense semi-algebraic subset

U

\mathscr {U}

of

L
(

R

n

,

R

m

)

L(\mathbb {R}^n, \mathbb {R}^m)

, the space of all linear mappings from

R

n

\mathbb {R}^n

to

R

m

\mathbb {R}^m

, such that for all

F
∈

U

F \in \mathscr {U}

, the image

(
F
+
G
)
(
X
)

(F + G)(X)

is a closed (semi-algebraic) set in

R

m

\mathbb {R}^m

. To do this, we study the tangent cone at infinity

C
∞

X

C_\infty X

and the set

E
∞

X
⊂

C
∞

X

E_\infty X \subset C_\infty X

of (unit) exceptional directions at infinity of

X
X

. Specifically we show that the set

E
∞

X

E_\infty X

is nowhere dense in

C
∞

X
∩

S

n
−
1

C_\infty X \cap \mathbb {S}^{n - 1}

.
𝐴_{∞} condition for general bases revisited: Complete classification of definitions
Authors: Kosz Dariusz
Published: June 2022

We refer to the discussion on different characterizations of the

A
∞

A_\infty

class of weights, initiated by Duoandikoetxea, Martín-Reyes, and Ombrosi [Math. Z. 282 (2016), pp. 955–972]. Twelve definitions of the

A
∞

A_\infty

condition are considered. For cubes in

R

d

\mathbb {R}^d

every two conditions are known to be equivalent, while for general bases we have a trichotomy: equivalence, one-way implication, or no dependency may occur. In most cases the relations between different conditions have already been established. Here all the unsolved cases are treated and, as a result, a full diagram of the said relations is presented.
The numerical solution of semidiscrete linear evolution problems on the finite interval using the Unified Transform Method
Authors: Cisneros Jorge , Deconinck Bernard
Published: June 2022

We study a semidiscrete analogue of the Unified Transform Method introduced by A. S. Fokas, to solve initial-boundary-value problems for linear evolution partial differential equations with constant coefficients on the finite interval

x
∈
(
0
,
L
)

x \in (0,L)

. The semidiscrete method is applied to various spatial discretizations of several first and second-order linear equations, producing the exact solution for the semidiscrete problem, given appropriate initial and boundary data. From these solutions, we derive alternative series representations that are better suited for numerical computations. In addition, we show how the Unified Transform Method treats derivative boundary conditions and ghost points introduced by the choice of discretization stencil and we propose the notion of “natural” discretizations. We consider the continuum limit of the semidiscrete solutions and compare with standard finite-difference schemes.
Collagenase Clostridium histolyticum for the Treatment of Cellulite in the Buttocks and Thigh: Early Insights From Clinical Practice
Authors: Graivier Miles , Hill David , Katz Bruce , Boehm Kristin A , Fisher Juliya , Battista China
Published: June 2022

Background

Collagenase Clostridium histolyticum (CCH-aaes; QWO [Endo Aesthetics, Malvern, PA]) is an injectable, enzyme-based treatment indicated for the treatment of moderate to severe cellulite on the buttocks of adult women. The minimally invasive nature of the treatment makes it an attractive option for targeted disruption of the fibrous septae which give rise to the dimples characteristic of cellulite in buttocks and thighs.

Objectives

The article provides an overview of cellulite treatment with CCH-aaes, including patient identification and education, treatment planning, CCH-aaes dilution, injection technique, safety, and early experience with mitigation of adverse events, including bruising.

Methods

As part of a continuing medical education (CME; xMedica, Alpharetta, GA) event on developments in cellulite treatment, a panel of experts developed a course and roundtable, which included lectures on cellulite physiology, new developments in the field of cellulite treatment, demonstrations of injection technique for CCH-aaes, and a review of considerations for the use of CCH-aaes in real-world clinical practice.

Results

The practical guidance presented here is based upon real-world experience with CCH-aaes. The discussion includes strategies based on early experience for how to obtain the best results as well as suggestions on how to mitigate bruising.

Conclusions

CCH-aaes has been a welcome addition to the armamentarium for the treatment of cellulite. With knowledge of proper patient evaluation and injection technique, thorough patient education, diligent photography, and developing research on bruising mitigation, CCH-aaes shows great promise as an effective and safe modality for the management of cellulite.

Level of Evidence: 5
Actions of DKK1 on the preimplantation bovine embryo to affect pregnancy establishment, placental function, and postnatal phenotype
Authors: Amaral Thiago F , Gonella-Diaza Angela , Heredia Daniella , Melo Gabriela D , Estrada-Cortés Eliab , Jensen Laura M , Pohler Ky , Hansen Peter J
Published: June 2022

One mechanism by which the maternal environment regulates the early embryo is by secretion of cell-signaling molecules. One of these is dickkopf WNT signaling pathway inhibitor 1. Objectives were to (A) resolve discrepancies in the literature regarding effects of dickkopf WNT signaling pathway inhibitor 1 in the bovine embryo on development of trophectoderm and competence to establish pregnancy after embryo transfer and (B) determine whether there are long-term consequences of dickkopf WNT signaling pathway inhibitor 1 on placental function and postnatal phenotype. Embryos produced in vitro were cultured with vehicle or 100 ng/mL recombinant human dickkopf WNT signaling pathway inhibitor 1 from Days 5 to 7.5 of development (i.e., the morula and blastocyst stages of development). dickkopf WNT signaling pathway inhibitor 1 increased the number of cells positive for the trophectoderm marker CDX2 at Day 7.5 of development while having no effect on number of cells positive for the inner cell mass marker SOX2. There was no effect of dickkopf WNT signaling pathway inhibitor 1 on pregnancy or calving rate after transfer of blastocysts produced with Y-sorted semen to either lactating dairy cows or suckling beef cows. Treatment with dickkopf WNT signaling pathway inhibitor 1 at the morula-to-blastocyst stages programmed placental function, as measured by an effect of dickkopf WNT signaling pathway inhibitor 1 on plasma concentrations of pregnancy associated glycoproteins and placental lactogen at Day 160 of gestation (although not on other days examined). dickkopf WNT signaling pathway inhibitor 1 treatment also resulted in calves that were heavier at birth as compared to calves derived from control embryos. After birth, dickkopf WNT signaling pathway inhibitor 1 calves grew slower than controls. Results confirm that dickkopf WNT signaling pathway inhibitor 1 alters the developmental program of the bovine embryo to affect both prenatal and postnatal phenotypes.
The Versatility of Simplicity: Structures of Cardiocephaloides longicollis Used for Different Purposes during Cercarial Transmission
Authors: van Beest G S , Montero F E , Padrós F , Raga J A , Born-Torrijos A
Published: June 2022

Synopsis

Transmission and infection strategies are critical for completing the life cycles of trematode parasites, which are characterized by complex life cycles involving multiple hosts and stages. Transmission between the first and second intermediate hosts typically relies on cercariae, a free-swimming larval stage that displays a series of behaviors to efficiently disperse, locate, attach to, and infect the next host. The aim of this study is to provide detailed information on behaviors used by furcocercariae (bifurcated tail) during its transmission from the snail to the fish host, using the laboratory-established model of Cardiocephaloides longicollis (Strigeidae). These cercariae are released from snails into seawater, where they swim, locate, penetrate the skin of fish, and encyst as metacercariae in their brain. In a series of in vivo assays, freshly-emerged cercariae were used to visually study their behavior and locomotion. Histopathology of experimentally infected gilthead seabreams with C. longicollis, taken at sequential post-infections times, were analysed to localize the migrating cercariae to the fish brain. Our results show that simplicity and versatility are the key features for the success of cercariae transmission by using their organs for different purposes. While 80 % of the behavior was spent in a resting position, the most common swimming behavior was with tail-first, which is commonly described in furcocercariae to reach the host microhabitat. However, C. longicollis relies more on the furcae of the tail by using them as a propeller providing thrust and guidance when they swim, instead of using the tail stem. After attaching to the fish skin, cercariae rapidly creep on it using the oral- and ventral-suckers simulating a leech-like movement until they find a suitable penetration site. To penetrate, cercariae press the cephalic structures against the skin, while the ventral-sucker anchors the cercariae to it. After this, they switch their locomotion to a slow peristaltic movement, opening the path through tissues with the help of their cephalic structures and anchoring their body with their surface spines. This is consistent with the post-penetration histological analyses, which suggested that C. longicollis cercariae move between the cells of the connective tissue and muscle fibers when migrating towards the fish's brain, without provoking relevant tissue damage or host responses. Understanding the versatility of cercarial structures to adapt to external conditions enriches our knowledge on parasites and their transmission ecology, opening the door to the design of avoidance methods in fish farms struggling with harmful parasites.
Verification of permeability for ionic liquid into biological specimens by using a mass spectrometer
Authors: Yamashita Taiji , Miyamoto Kenji , Yonenobu Hitoshi
Published: June 2022

The pretreatment method with ionic liquids (ILs) is convenient for scanning electron microscope (SEM) observation of biological specimens. It needs neither fixation nor vacuum vapor deposition of metals to prevent fracture, deformation and charge-up. Although it was pointed out that the reason why the specimens are not fractured or deformed under the vacuum without fixation is the penetration of the ILs into cells and replacement with the intercellular water of the specimen, the experimental results were not yet self-consistent. In this study, in order to verify this hypothesis, we investigated whether the components of 1-ethyl-3-methylimidazolium methylphosphonate ([EMIM][MePO3]) are detectable by using a time-of-flight secondary ion mass spectrometer (TOF-SIMS) and liquid chromatography. It was found that the components of [EMIM][MePO3] could be detected from inside of the biological specimens. Moreover, it was verified that there is no fracture and deformation of the specimen, whose residual concentration of the IL on the surface would be less than the limit of detection by TOF-SIMS. Therefore, these experimental results explicitly show that penetration of [EMIM][MePO3] into the specimen and subsequent replacement with the intercellular water inside the body is the reason for preventing fracture and deformation of the specimen under the vacuum.
What are the spectroscopic binaries with high-mass functions near the Gaia DR3 main sequence?
Authors: El-Badry Kareem , Rix Hans-Walter
Published: June 2022

The third data release of the Gaia mission includes orbital solutions for >105 single-lined spectroscopic binaries, representing more than an order of magnitude increase in sample size over all previous studies. This data set is a treasure trove for searches for quiescent black hole + normal star binaries. We investigate one population of black hole candidate binaries highlighted in the data release: sources near the main sequence in the colour–magnitude diagram (CMD) with dynamically inferred companion masses M2 larger than the CMD-inferred mass of the luminous star. We model light curves, spectral energy distributions, and archival spectra of the 14 such objects in DR3 with high-significance orbital solutions and inferred $M_2 \gt 3\, {\rm M}_{\odot }$. We find that 100 per cent of these sources are mass-transfer binaries containing a highly stripped lower giant donor (0.2 ≲ M/M⊙ ≲ 0.4) and much more massive (2 ≲ M/M⊙ ≲ 2.5) main-sequence accretor. The Gaia orbital solutions are for the donors, which contribute about half the light in the Gaia RVS bandpass but only $\lesssim 20{{\ \rm per\ cent}}$ in the g band. The accretors’ broad spectral features likely prevented the sources from being classified as double-lined. The donors are all close to Roche lobe filling ($R/R_{\rm Roche\, lobe}\gt 0.8$), but modelling suggests that a majority are detached ($R/R_{\rm Roche\, lobe}\lt 1$). Binary evolution models predict that these systems will soon become detached helium white dwarf + main-sequence ‘EL CVn’ binaries. Our investigation highlights both the power of Gaia data for selecting interesting subpopulations of binaries and the ways in which binary evolution can bamboozle standard CMD-based stellar-mass estimates.
A Phylogenomic Backbone for Gastropod Molluscs
Authors: Uribe Juan E , González Vanessa L , Irisarri Iker , Kano Yasunori , Herbert David G , Strong Ellen E , Harasewych M G
Published: June 2022

Gastropods have survived several mass extinctions during their evolutionary history resulting in extraordinary diversity in morphology, ecology, and developmental modes, which complicate the reconstruction of a robust phylogeny. Currently, gastropods are divided into six subclasses: Caenogastropoda, Heterobranchia, Neomphaliones, Neritimorpha, Patellogastropoda, and Vetigastropoda. Phylogenetic relationships among these taxa historically lack consensus, despite numerous efforts using morphological and molecular information. We generated sequence data for transcriptomes derived from 12 taxa belonging to clades with little or no prior representation in previous studies in order to infer the deeper cladogenetic events within Gastropoda and, for the first time, infer the position of the deep-sea Neomphaliones using a phylogenomic approach. We explored the impact of missing data, homoplasy, and compositional heterogeneity on the inferred phylogenetic hypotheses. We recovered a highly supported backbone for gastropod relationships that is congruent with morphological and mitogenomic evidence, in which Patellogastropoda, true limpets, are the sister lineage to all other gastropods (Orthogastropoda) which are divided into two main clades 1) Vetigastropoda $s.l.$ (including Pleurotomariida $+$ Neomphaliones) and 2) Neritimorpha $+$ (Caenogastropoda $+$ Heterobranchia). As such, our results support the recognition of five subclasses (or infraclasses) in Gastropoda: Patellogastropoda, Vetigastropoda, Neritimorpha, Caenogastropoda, and Heterobranchia. [Compositional heterogeneity; fast-evolving; long-branch attraction; missing data; Mollusca; phylogenetics; systematic error.]
Production cow-calf responses from perennial forage-based and integrated beef-cropping systems
Authors: Carlson Zac E , McPhillips Levi J , Erickson Galen E , Drewnoski Mary E , MacDonald Jim C
Published: June 2022

An experiment was conducted to measure production responses of an alternative cow-calf production system integrated into a cropping system without access to perennial forage compared to a traditional cow-calf system utilizing perennial forage. Multiparous, cross-bred beef cows (n = 160; average age = 6.2 ± 2.8 yr) were utilized in a randomized complete block experimental design and unstructured treatment design. Upon initiation, cows were blocked by age and stratified by source, assigned randomly to one of two production systems, each with four replicates (n = 20 cows/replicate). Once allotted to their treatment groups, cows remained in their experimental units for the duration of the experiment. Treatments were: 1) a traditional system consisting of April to May calving with smooth bromegrass pasture and grazed corn residue as forage resources (TRAD); 2) an alternative system consisting of July to August calving utilizing partial-drylot feeding, summer-planted oats, and corn residue grazing (ALT). There were no differences (P ≥ 0.27) in calving rates (91.8 vs. 86.7 ± 2.92%), pregnancy rates (89.3 vs. 89.9 ± 2.66%), and weaning rates (87.2 vs. 82.3 ± 3.29%) for TRAD vs. ALT, respectively. However, there was an increase (P = 0.04) in the rate of twin offspring in ALT (2.9 vs. 9.4 ± 2.36% for TRAD vs. ALT, respectively). One calf from the set of twins was selected randomly at birth to be removed from the experiment, so the production data are only from single calves. There was no difference (P = 0.47) in calf body weight at birth (40 vs. 39 ± 0.7 kg for TRAD vs. ALT, respectively). At weaning, calves in the ALT system were lighter (P < 0.01) at the same day of age (184 vs. 229 ± 5.5 kg) compared to TRAD calves. Cows from the ALT system had fewer (P < 0.01) kg weaned per cow exposed to bull (150 vs. 199 ± 7.2 kg) compared to TRAD cows. Apart from the twinning rate, no differences in reproductive performance were observed among systems. However, reduced weaning weights and kilogram of weaned calf per cow exposed may negatively impact revenue to the cow-calf enterprise of the ALT system.
Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring: A Nationwide Cohort Study
Authors: Wensink Maarten J. , Lu Ying , Tian Lu , Shaw Gary M. , Rizzi Silvia , Jensen Tina Kold , Mathiesen Elisabeth R. , Skakkebæk Niels E. , Lindahl-Jacobsen Rune , Eisenberg Michael L.
Published: June 2022

(Abstracted from Ann Intern Med 2022;175:665–673)

Diabetes mellitus is known to compromise sperm quality and is associated with impaired male fertility. Metformin is a first-line oral diabetes medication that has been shown to improve markers of semen quality in obese men but reduces serum testosterone levels independently of glycemic control.
Impact of Using Abdominal Circumference Independently in the Diagnosis of Fetal Growth Restriction
Authors: Pressman Katherine , Odibo Linda , Duncan Jose R. , Odibo Anthony O.
Published: June 2022

(Abstracted from J Ultrasound Med 2022;41:157–162)

Screening for fetal growth restriction (FGR) to identify those fetuses at increased risk of adverse neonatal outcomes has been difficult. Investigators have defined FGR in different ways, which has complicated efforts to validate results.
The Frequency and Outcomes of Nerve Palsies in Operatively Treated Supracondylar Humerus Fractures
Authors: Norrell Kirsten N. , Muolo Connor E. , Sherman Ashley K. , Sinclair Micah K.
Published: June 2022

Background:

A high index of suspicion for nerve palsy is essential in the setting of a displaced supracondylar humerus fracture (SCHF) with careful attention to the examination. We hypothesize that nerve injuries are more prevalent in higher energy type III and flexion SCHFs compared with type II fractures.

Methods:

A retrospective review was performed of 1085 operatively treated SCHFs in pediatric patients, aged 0 to 14 years, between January 1, 2015 and December 31, 2018. There were 979 patients eligible for analysis. Exclusion criteria included follow-up <3 weeks, polytrauma, pathologic fracture, and prior fracture of the ipsilateral elbow.

Results:

The overall rate of nerve injury was 10.6% (104/979). A significant difference in the rate of nerve palsy was identified between fracture types: 0.9% type II, 19.3% type III, and 10.7% flexion type SCHFs (P<0.001). Median nerve palsy was the most common (n=65). An increased rate of ulnar nerve palsy was observed in flexion type SCHFs. The rate of nerve palsy was higher in the medial pin group (14.9%, P=0.035) but no significant association with iatrogenic ulnar nerve palsy was present. In type III and flexion SCHFs, operative time >60 minutes (P=0.023) and the need for open reduction (P=0.012) were significantly associated with postoperative nerve palsy. Referral to therapy was required in 30.8% of patients with a nerve palsy compared with 7.9% of patients without (P<0.001).

Conclusion:

Longer operative times, need for open reduction, and significantly higher rates of nerve palsy among type III and flexion SCHFs are best explained by the unstable nature of the fracture and greater degree of soft tissue trauma. Given prolonged duration of follow-up and more frequent need for therapy demonstrated in patients with a nerve palsy, these data can be used to improve counseling for families and patients after displaced SCHF.

Level of Evidence:

Level III—retrospective comparative study.
Metabolic Regulation of Hematopoietic Stem Cells
Authors: Morganti Claudia , Cabezas-Wallscheid Nina , Ito Keisuke
Published: June 2022

Cellular metabolism is a key regulator of hematopoietic stem cell (HSC) maintenance. HSCs rely on anaerobic glycolysis for energy production to minimize the production of reactive oxygen species and shift toward mitochondrial oxidative phosphorylation upon differentiation. However, increasing evidence has shown that HSCs still maintain a certain level of mitochondrial activity in quiescence, and exhibit high mitochondrial membrane potential, which both support proper HSC function. Since glycolysis and the tricarboxylic acid (TCA) cycle are not directly connected in HSCs, other nutrient pathways, such as amino acid and fatty acid metabolism, generate acetyl-CoA and provide it to the TCA cycle. In this review, we discuss recent insights into the regulatory roles of cellular metabolism in HSCs. Understanding the metabolic requirements of healthy HSCs is of critical importance to the development of new therapies for hematological disorders.
Predicting the risk of clinically significant intraocular lens tilt and decentration in vitrectomized eyes
Authors: Zhang Jiaqing , Han Xiaotong , Zhang Miao , Liu Zhenzhen , Chen Xiaoyun , Qiu Xiaozhang , Lin Haowen , Li Jiaqing , Liu Bingqian , Zhang Chun , Wei Yantao , Jin Guangming , Tan Xuhua , Luo Lixia
Published: June 2022

Purpose:

To identify predictors and develop a prognostic nomogram for clinically significant intraocular lens (IOL) tilt and decentration in vitrectomized eyes.

Setting:

Zhongshan ophthalmic center, Guangzhou, China.

Design:

Prospective observational study.

Methods:

Patients with previous pars plana vitrectomy who underwent phacoemulsification with IOL implantation were enrolled in this study. The tilt and decentration of the lens and IOL were assessed by a swept-source anterior segment optical coherence tomography (CASIA2). Multiple logistic regression analysis and prognostic nomogram models were used to explore factors associated with clinically significant IOL tilt and decentration (defined as tilt ≥7 degrees and decentration ≥0.4 mm).

Results:

375 patients (375 eyes) with a mean age of 56.1 ± 9.81 years were included. Lens tilt (odds ratio [OR] = 1.44), lens decentration (OR = 1.74), lens diameter (OR = 0.49), and hydrophilic IOL (OR = 2.36) were associated with IOL tilt over 7 degrees (all P < .05). Lens tilt (OR = 1.24), lens decentration (OR = 2.30), and incomplete capsulorhexis–IOL overlap (OR = 2.44) increased the risk of IOL decentration over 0.4 mm (all P < .05). Preoperative lens tilt together with lens decentration was identified as the strongest predictor of incident clinically significant IOL tilt (area under the curve [AUC] = 0.82, 95% CI, 0.76-0.88) and decentration (AUC: 0.84, 95% CI, 0.78-0.89), and the nomogram was constructed accordingly.

Conclusions:

The tilt and decentration of the crystalline lens, hydrophilic IOL, and incomplete capsulorhexis–IOL overlap were risk factors for clinically significant IOL misalignment. Clinicians could use a prognostic nomogram model based on the preoperative lens position to make a strategy for higher-risk patients.
The Effect of Intradialytic Range of Motion Exercise on Dialysis Adequacy and Fatigue in Hemodialysis Patients
Authors: MALINI Hema , FORWATY Erni , CLEARY Michelle , VISENTIN Denis , OKTARINA Elvi , LENGGOGENI Devia Putri
Published: June 2022

Background

Many hemodialysis patients experience fatigue as a result of not achieving dialysis adequacy.

Purpose

This study was designed to determine the effect of intradialytic range-of-motion exercises on dialysis adequacy and fatigue in patients undergoing hemodialysis.

Methods

In this two-arm experimental study with repeated measures, participants were allocated to treatment (n = 25, 23 completed) and control (n = 25, 24 completed) groups using computerized simple random sampling. Participants in the treatment group performed 30-minute weekly intradialytic exercise sessions in addition to receiving standard care, whereas those in the control group received standard care only.

Results

Fatigue and dialysis characteristics were reported at baseline, at the midpoint (end of Week 4), and at the end of Week 8. Whereas mean Kt/V (dialysis adequacy) and urea reduction ratio increased and the fatigue level decreased in the treatment group, these variables did not change in the control group. Significant mean differences in Kt/V, urea reduction ratio, and fatigue between the groups were observed at the end of Week 8.

Conclusions

Intradialytic range-of-motion exercises are recommended for patients undergoing hemodialysis to increase dialysis adequacy and reduce fatigue.
The Psychological Benefits of Cosmetic Surgery
Authors: Kam Olivia , Na Sean , La Sala Michael , Tejeda Christina I. , Koola Maju Mathew
Published: June 2022

The objective of this review is to shed light on the literature regarding the psychological impact of invasive cosmetic surgery and to discuss future implications for research and clinical practice. Articles published through October 2021 were reviewed to answer the question, “Does cosmetic surgery improve a patient's overall psychological health?” Psychological well-being was examined through the lens of body image, self-esteem, anxiety, and depression scores. The studies revealed that although cosmetic surgery seems to boost patients' body image, other crucial aspects of psychological well-being may or may not similarly benefit. Notably, factors such as a patient's preoperative mental status, level of education, type of cosmetic procedure, postoperative healing time, sex, and age play a role in determining the direction and magnitude of psychological change after surgery. Limitations include the lack of diversity in study populations and the potential role of body dysmorphic disorder. Overall, researchers have concluded that cosmetic surgery improves body image but remain in disagreement on its effects on self-esteem, anxiety, and depression.
The Use and Safety of Leave From an Acute Inpatient Psychiatry Unit
Authors: Hristidis Vasilis C. , Cáceda Ricardo , Kim Ji Soo , Bronson Brian , Hill Emily A.
Published: June 2022

Leave passes provide authorized leave for hospitalized patients from a psychiatric inpatient unit. Although providing day passes was once a relatively common practice, there are relatively few data describing their safety and efficacy. This descriptive study examines the use of leave passes in an adult inpatient unit at a university hospital between 2017 and 2021, with attention to reasons for granting the day pass, duration, and outcome of the pass. During the study period, 10 patients with primary psychotic or mood disorders received 12 passes for housing coordination, COVID-19 vaccination, or major family events. There were no fatalities or abscondments. One patient experienced severe agitation and engaged in nonsuicidal self-injurious behavior. A second patient showed mild, redirectable psychomotor agitation upon return to the unit. The remaining 10 passes were uneventful. Our findings support the view that patients with diverse diagnoses can safely be provided leave from an inpatient setting with adequate planning and support, yielding a low incidence of adverse events.
Reduced Reproductive Success Is Associated With Selective Constraint on Human Genes
Authors: Gardner Eugene J. , Neville Matthew D. C. , Samocha Kaitlin E. , Barclay Kieron , Kolk Martin , Niemi Mari E. K. , Kirov George , Martin Hilary C. , Hurles Matthew E.
Published: June 2022

(Abstracted from Nature 2022;603:858–863)

The genetic variants, gene deletions, and protein-truncating variants (PTVs) with the most significant negative effect are removed from the population by selection with strength that varies substantially between genes. A subset of approximately 3000 genes has been studied because they carry the highest probability of loss-of-function intolerance.
Outcomes of Single-Dose Empirical Antibiotic Treatment in Children With Suspected Sepsis Implemented in the Emergency Department
Authors: Khanthathasiri Suwimon , Kriengsoontornkij Worapant , Monsomboon Apichaya , Phongsamart Wanatpreeya , Lapphra Keswadee , Wittawatmongkol Orasri , Rungmaitree Supattra , Chokephaibulkit Kulkanya
Published: June 2022

Objectives

Implementing a single-dose empirical antibiotic (SDEA) strategy at the emergency department (ED) in children with suspected sepsis may improve outcomes. We aim to evaluate the outcomes of the SDEA strategy for children with suspected sepsis at the ED in a tertiary care center in Bangkok.

Methods

Children who met the predefined checklist screening criteria for suspected sepsis were administered single-dose intravenous cefotaxime 100 mg/kg, or meropenem 40 mg/kg if they were immunocompromised or recently hospitalized. The medical records of children diagnosed with sepsis and septic shock caused by bacterial or organ-associated bacterial infections before and after implementation of the SDEA strategy were reviewed.

Results

A total of 126 children with sepsis before and 127 after implementation of the SDEA strategy were included in the analysis. The time from hospital arrival to antibiotic initiation was significantly reduced after implementation of the SDEA strategy: median, 241 (110–363) minutes before versus 89 (62–132) minutes after (P < 0.001), with an increased number of patients starting antibiotics within 3 hours of hospital arrival: 42.1% vs 85.0% (P < 0.001). Comparing before and after SDEA implementation, children receiving SDEA had a shorter median duration of antibiotic therapy: 7 (5–13.3) versus 5 (3–7) days (P = 0.001), shorter length of hospital stay: 10 (6–16.3) versus 7 (4–11) days (P = 0.001), and fewer intensive care unit admissions: 30 (23.8%) versus 17 (13.4%; P = 0.036); however, mortality was not different: 3 (2.4%) in both groups. In multivariate analysis, SDEA strategy was the independent factor associated with reduced intensive care unit admission or death. Adherence to SDEA was 91.4%. Single-dose empirical antibiotic was retrospectively considered not necessary for 22 children (11.9%), mostly diagnosed with viral infections afterward.

Conclusions

Single-dose empirical antibiotic at the ED is an effective strategy to reduce the time from hospital arrival to antibiotic initiation and can help improve outcomes of sepsis in children.
Pediatric Emergency Medicine Physicians' Perceptions of Colleagues' Clinical Performance Over Career Span
Authors: Henretig Fred M. , Wood Joanne N. , Shea Judy A. , Schapira Marilyn M. , Ruddy Richard M.
Published: June 2022

Objective

The US physician workforce is aging, prompting concerns regarding clinical performance of senior physicians. Pediatric emergency medicine (PEM) is a high-acuity, multitasking, diagnostically complex and procedurally demanding specialty. Aging's impact on clinical performance in PEM has not been examined. We aimed to assess PEM physician's' perceptions of peers' clinical performance over career span.

Methods

We surveyed 478 PEM physician members of the American Academy of Pediatrics' Section on Emergency Medicine survey study list-serve in 2020. The survey was designed by the investigators with iterative input from colleagues. Respondents rated, using a 5-point Likert scale, the average performance of 4 age categories of PEM physicians in 9 clinical competencies. Additional items included concerns about colleague's performance and preferences for age of physician managing a critically ill child family member.

Results

We received 232 surveys with responses to core initial items (adjusted response rate, 49%). Most respondents were 36 to 49 (34.9%) or 50 to 64 (47.0%) years old. Fifty-three percent reported ever having concern about a colleague's performance. For critical care–related competencies, fewer respondents rated the ≥65-year age group as very good or excellent compared with midcareer physicians (36–49 or 50–64 years old). The ratings for difficult communications with families were better for those 65 years or older than those 35 years or younger. Among 129 of 224 respondents (58%) indicating a preferred age category for a colleague managing a critically ill child relative, most (69%) preferred a 36 to 49-year-old colleague.

Conclusions

Pediatric emergency medicine physicians' perceptions of peers' clinical performance demonstrated differences by peer age group. Physicians 65 years or older were perceived to perform less well than those 36 to 64 years old in procedural and multitasking skills. However, senior physicians were perceived as performing as well if not better than younger peers in communication skills. Further study of age-related PEM clinical performance with objective measures is warranted.
A New Baseline: Master of Public Health Education Shifting to Meet Public Health Needs
Authors: Meredith Genevive R. , Welter Christina R. , Risley Kris , Seweryn Steven M. , Altfeld Susan , Jarpe-Ratner Elizabeth A.
Published: June 2022

Context:

Schools and programs of public health have been preparing graduates to join the workforce for a century, but significant gaps in numbers and abilities exit. Many have called for a change to the status quo, to transform public health education to create a competent workforce able to address current and emergent needs.

Objective:

This study explored if Master of Public Health (MPH) programs have shifted their program design, curriculum, and/or instructional methods (instructional design), and if so, how and why.

Design:

A sequential mixed-methods study.

Setting:

MPH programs accredited by the Council on Education for Public Health, and approved applicants.

Participants:

Some 43% of accredited MPH programs in the United States (n = 115) responded to the online survey (open November 21, 2019-December 20, 2019), providing a representative sample. Stratified purposeful sampling was used to select 8 MPH programs for follow-up semistructured interviews. Categorical and qualitative data were analyzed for trends, association, and themes.

Main Outcome Measures:

Degree of, types of, and reasons for shifts in MPH program instructional design considered and implemented.

Results:

MPH programs in the United States have shifted their approaches and curriculum to meet identified and emergent workforce needs. In the last 5 years, 81% made changes to program design (focal competencies, admissions, graduation criteria), 88% to curriculum (added or removed courses, changed course content), and 65% to pedagogical methods (where and how learning is supported).

Conclusions:

Despite concerns about stagnation, MPH programs have shifted to competency-based education aligned with workforce needs, have adapted approaches to support diversity of future workers, and are focused on bolstering workforce readiness. These changes were made to enhance focus on knowledge acquisition, skills building, and professionalism, factors recognized as critical for success, and facilitate more engaged pedagogical strategies, working with communities for impact.
Bmp5 Mutation Alters circRNA Expression During Embryonic External Ear Development
Authors: Liu Wei , Lin Lin , Wang Qiushi , Yang Qinghua , Jiang Haiyue
Published: June 2022

Bmp5 mutation can lead to microtia in mice models; however, its underlying mechanism is unclear. We analyzed circular RNA (circRNA) expression changes and associated gene regulation during embryonic development of the mouse’s external ear after a point mutation occurred naturally in the BMP5 gene. The outer ear tissues of BMP5 short-eared mouse model embryos at embryonic day (E) 15.5 and E17.5 were subjected to RNA sequencing. Changes in the circRNA expression profile were detected using find_circ and the CiRi2 software. Differentially expressed circRNAs were annotated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The circRNA expression profile differed between wild-type and mutant mouse embryos. At E15.5, differentially expressed RNAs were involved in the Hippo signaling pathway, whereas those at E17.5 were associated with stem cell pluripotency. Therefore, circRNA is involved in regulating embryonic external ear development, thus providing a basis for studying the biological aspect of its regulation.
Bioresorbable Implants in Reduction of Paediatric Zygomaticomaxillary Complex Fractures Concurrent With Internal Orbital Reconstruction
Authors: Zhao Yiping , Sun Jing , Li Zhengkang , Deng Yuan
Published: June 2022

Purpose:

To evaluate the clinical effectiveness and safety of bioresorbable implants for treating paediatric zygomaticomaxillary complex (ZMC) fractures with concomitant orbital floor defects.

Methods:

A retrospective review of paediatric patients who underwent ZMC repair with concomitant orbital floor fractures with bioresorbable implants in Shanghai Ninth People’s Hospital from July 2015 to June 2019 was performed. The primary outcome measures included ocular motility, diplopia, enophthalmos, facial deformities, and restricted mouth opening, as well as complication rates. Pre- and post-operative computed tomography scans were obtained for clinical diagnosis and surgical effectiveness.

Results:

Twenty two children were included in this study. Facial deformities were corrected in all 22 cases by surgical reconstruction postoperatively, and the average relative distance of Portals point-Zygomaxillare and Anteriornasalspine-Zygomaxillare were 1.3 ± 0.6mm (P = 0.22) and 1.2 ± 0.5mm (P = 0.19). The eye movement restored to normal in 13 patients. The mean amount of relative enophthalmos was 1.0 ± 0.4 mm (P = 0.12). 12 cases had complete resolution of diplopia postoperatively at the extremes of the gaze, and 1 case presented persistent diplopia on the down gaze as before, but from level III to level I. Facial numbness was resolved completely in 6 cases, and 2 cases presented with persistent numbness but relieved significantly. The average Hounsfield units of RapidSorb plates and OrbFloor PI were 154 ± 5 and 99 ± 4 respectively on computed tomography image obtained 1 week postoperatively, which showed no obvious difference compared with 0.5 year postoperatively (P > 0.1). Hounsfield units of implants gradually declined around 1 year postoperatively. Hounsfield units of RapidSorb plates (20 ± 1) were consistent with periorbital tissue during postoperative 2-year follow-up, and Hounsfield units of OrbFloor PI (19 ± 1) were consistent with periorbital tissue during postoperative 1.5-year follow-up. No patients had severe sequelae or implant related complications postoperatively. None of bone nonunion, malunion, infection or rejection occurred during the follow-up periods.

Conclusions:

Open reduction and internal fixation for the treatment of ZMC fracture have achieved significant improvement in functional and cosmetic outcomes postoperatively. Bioresorbable materials have been proved to be effective and safe in the treatment of children’s ZMC and orbital wall fractures.
Orthopedic Surgery Causes Gut Microbiome Dysbiosis and Intestinal Barrier Dysfunction in Prodromal Alzheimer Disease Patients
Authors: Liu Fangyan , Duan Mei , Fu Huiqun , Zhao Guoguang , Han Ying , Lan Fei , Ahmed Zara , Cao Guanglei , Li Zheng , Ma Daqing , Wang Tianlong
Published: June 2022

Objective:

To investigate gut microbiota and intestinal barrier function changes after orthopedic surgery in elderly patients with either normal cognition (NC) or a prodromal Alzheimer disease phenotype (pAD) comprising either subjective cognitive decline (SCD) or amnestic mild cognitive impairment (aMCI).

Background:

Homeostatic disturbances induced by surgical trauma and/or stress can potentially alter the gut microbiota and intestinal barrier function in elderly patients before and after orthopedic surgery.

Methods:

In this prospective cohort study, 135 patients were subject to preoperative neuropsychological assessment and then classified into: NC (n=40), SCD (n=58), or aMCI (n=37). Their gut microbiota, bacterial endotoxin (lipopolysaccharide), tight junction (TJ) protein, and inflammatory cytokines in blood were measured before surgery and on postsurgical day 1, 3, and 7 (or before discharge).

Results:

The short-chain fatty acid (SCFA)-producing bacteria were lower while the gram-negative bacteria, lipopolysaccharide and TJ were higher preoperatively in both the SCD and aMCI (pAD) groups compared with the NC group. After surgery, a decrease in SCFA-producing bacteria, and an increase in both gram-negative bacteria and plasma claudin were significant in the pAD groups relative to the NC group. SCFA-producing bacteria were negatively correlated with TJ and cytokines in pAD patients on postsurgical day 7. Furthermore, surgery-induced perioperative metabolic stress and inflammatory responses were associated with gut microbiota alterations.

Conclusions:

Surgery exacerbates both preexisting microbiota dysbiosis and intestinal barrier dysfunction in pAD patients, all of which may be associated with systemic inflammation and, in turn, may lead to further cognitive deterioration.
Intentional Watch and Wait or Organ Preservation Surgery Following Neoadjuvant Chemoradiotherapy Plus Consolidation CAPEOX for MRI-defined Low-risk Rectal Cancer
Authors: Wang Lin , Zhang Xiao-Yan , Zhao Yi-Ming , Li Shi-Jie , Li Zhong-Wu , Sun Ying-Shi , Wang Wei-Hu , Wu Ai-Wen ,   on behalf of The Rectal Cancer Cooperative Group of Peking University Cancer Hospital
Published: June 2022

Objective:

To assess the efficacy and safety of intentional watch and wait (W&W) and organ preservation surgery following neoadjuvant chemoradiotherapy plus consolidation CAPEOX in magnetic resonance imaging (MRI)-defined low-risk rectal cancer.

Background:

Clinical T2/early T3 rectal cancers can achieve high yield pathological complete response (ypCR) rates after chemoradiotherapy; thus, an intentional W&W or organ preservation strategy for good clinical responders in these subgroups can be further tested.

Methods:

This prospective, single-arm, phase 2 trial enrolled patients with low-risk MRI prestaged rectal cancers, who concurrently received chemoradiation, followed by four 3-weekly cycles of CAPEOX regimen. Following reassessment, clinical complete response (cCR) or near-cCR patients underwent W&W/organ preservation surgery; the primary endpoint was a 3-year organ preservation rate.

Results:

Of the 64 participants, 58 completed treatment, with 6.4% and 33.9% grade 3 to 4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively, during a median 39.5-month follow-up. Initial cCR, and non-cCR occurred in 33, 13, and 18 patients, respectively. Of the 31 cCR and 7 near-cCR cases managed by W&W, local regrowth occurred in 7; of these, 6 received salvage surgery. The estimated 2-year local regrowth rates were 12.9% [95% confidence interval (CI): 1.1%–24.7%] in cCR and 42.9% (95% CI: 6.2%–79.6%) in near-cCR cases, respectively. Eight patients received local excision, including 2 with regrowth salvage. Lung metastases occurred in 3 patients and multiple metastasis occurred in 1 patient; no local recurrence occurred. The estimated 3-year organ preservation rate was 67.2% (95% CI: 55.6%–78.8%). The estimated 3-year cancer-specific survival, non-regrowth disease-free survival, and stoma-free survival were 96.6% (95% CI: 92.1%–100%), 92.2% (95% CI: 85.5%–98.9%), and 82.7% (95% CI: 73.5%–91.9%), respectively.

Conclusions:

Chemoradiotherapy plus consolidation CAPEOX for MRI-defined low-risk rectal cancer can lead to high rates of organ preservation through intentional W&W or local excision. The oncologic safety of this strategy should be further tested.
Evaluation of Fontan-associated Liver Disease and Ethnic Disparities in Long-term Survivors of the Fontan Procedure
Authors: Emamaullee Juliet , Martin Sean , Goldbeck Cameron , Rocque Brittany , Barbetta Arianna , Kohli Rohit , Starnes Vaughn
Published: June 2022

Objectives:

Fontan-associated liver disease (FALD) has emerged as a nearly universal chronic comorbidity in patients with univentricular congenital heart disease who undergo the Fontan procedure. There is a paucity of data reporting long-term outcomes and the impact of FALD in this population.

Methods:

Patients who underwent the Fontan procedure between 1992 and 2018 were identified using California registry data. Presumed FALD was assessed by a composite of liver disease codes. Primary outcomes were mortality and transplant. Multivariable regression and survival analyses were performed.

Results:

Among 1436 patients post-Fontan, 75.9% studied were adults, with a median follow-up of 12.6 (8.4, 17.3) years. The population was 46.3% Hispanic. Overall survival at 20 years was >80%, but Hispanic patients had higher mortality risk compared with White patients [hazard ratio: 1.49 (1.09–2.03), P=0.012]. Only 225 patients (15.7%) had presumed FALD, although >54% of patients had liver disease by age 25. FALD was associated with later deaths [median: 9.6 (6.4–13.2) years post-Fontan] compared with patients who died without liver disease [4.1 (1.4–10.4) years, P=0.02]. Patients with FALD who underwent combined heart liver transplant had 100% survival at 5 years, compared with only 70.7% of patients who underwent heart transplant alone.

Conclusions:

In this population-based analysis of long-term outcomes post-Fontan, Hispanic ethnicity was associated with increased all-cause mortality. Further, the prevalence of FALD is underrecognized, but our data confirms that its incidence increases with age. FALD is associated with late mortality but excellent posttransplant survival. This emphasizes the need for FALD-specific liver surveillance strategies in patients post-Fontan.
Relatively Poor Long-term Outcomes Following Liver Transplantation for NASH in the United States
Authors: Jamil Omar K. , Sandikçi Burhaneddin , Faust Nolan , Cotter Thomas G. , Paul Sonali , di Sabato Diego , Fung John , Charlton Michael
Published: June 2022

Background.

Nonalcoholic steatohepatitis (NASH) continues to increase in frequency as an indication for liver transplantation (LT). Data on long-term outcomes for these patients are limited. We aimed to compare long-term patient and graft survival in patients undergoing LT for NASH in the United States to other indications.

Methods.

We analyzed data from the Scientific Registry of Transplant Recipients of adult patients who underwent primary deceased-donor LT from January 1, 2005, to December 31, 2019.

Results.

NASH has increased as an indication for LT by 4.5-fold, from 5.2% in 2005 to 23.4% in 2019. Patient (61.2%) and graft survival (59.2%) at 10 y are significantly poorer for NASH than for all other indications other than alcohol. Patients transplanted for NASH have higher body mass index (32.2 versus 27.6) and greater frequency of diabetes (13% versus 11.6%) than any other indication (P < 0.001). Portal vein thrombosis, location in intensive care unit, dialysis, and pre-LT diabetes (P < 0.001 for all) are independently predictive of patient death and graft loss. Body mass index is not predictive. NASH patients undergoing simultaneous liver kidney have markedly worse 10-y patient and graft survival than liver-only (52.3% versus 62.1%). Graft loss was attributed to recurrence of NASH in <1% of patients.

Conclusions.

LT for NASH is associated with relatively poor long-term patient and graft survival when compared with patients transplanted for other indications, NASH patients undergoing simultaneous liver kidney have the worst long-term outcomes.