bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstructing the universe with variational self-boosted sampling
Authors: Modi Chirag , Li Yin , Blei David
Published: March 2023

Forward modeling approaches in cosmology have made it possible to reconstruct the initial conditions at the beginning of the Universe from the observed survey data.
However the high dimensionality of the parameter space still poses a challenge to explore the full posterior, with traditional algorithms such as Hamiltonian Monte Carlo (HMC) being computationally inefficient due to generating correlated samples and the performance of variational inference being highly dependent on the choice of divergence (loss) function.
Here we develop a hybrid scheme, called variational self-boosted sampling (VBS)
to mitigate the drawbacks of both these algorithms by
learning a variational approximation for the proposal distribution of Monte Carlo sampling and combine it with HMC.
The variational distribution is parameterized as a normalizing flow and learnt with samples generated on the fly, while proposals drawn from it reduce auto-correlation length in MCMC chains.
Our normalizing flow uses Fourier space convolutions and element-wise operations to scale to high dimensions.
We show that after a short initial warm-up and training phase,
VBS generates better quality of samples than simple VI approaches and in the hybrid sampling phase, reduces the correlation length in the sampling phase by a factor of 10–50 over using only HMC to explore the posterior of initial conditions in 643 and 1283 dimensional problems, with larger gains for high signal-to-noise data observations. Hybrid sampling with online training of the variational distribution violates Markov property, and to retain the asymptotic guarantees of HMC, in the final phase we use a fixed variational distribution as proposal distribution and propagate these samples to the posterior distribution.
Advancing treatment of retinal disease through in silico trials
Authors: Hernandez Rémi J , Roberts Paul A , El-Bouri Wahbi K
Published: March 2023

Treating retinal diseases to prevent sight loss is an increasingly important challenge. Thanks to the configuration of the eye, the retina can be examined relatively easily in situ. Owing to recent technological development in scanning devices, much progress has been made in understanding the structure of the retina and characterising retinal biomarkers. However, treatment options remain limited and are often of low efficiency and efficacy. In recent years, the concept of in silico clinical trials (ISCTs) has been adopted by many pharmaceutical companies to optimise and accelerate the development of therapeutics. ISCTs rely on the use of mathematical models based on the physical and biochemical mechanisms underpinning a biological system. With appropriate simplifications and assumptions, one can generate computer simulations of various treatment regimens, new therapeutic molecules, delivery strategies and so forth, rapidly and at a fraction of the cost required for the equivalent experiments. Such simulations have the potential not only to hasten the development of therapies and strategies but also to optimise the use of existing therapeutics. In this paper, we review the state-of-the-art in in silico models of the retina for mathematicians, biomedical scientists and clinicians, highlighting the challenges to developing ISCTs. Throughout this paper, we highlight key findings from in silico models about the physiology of the retina in health and disease. We describe the main building blocks of ISCTs and identify challenges to developing ISCTs of retinal diseases.
Fabrication and applications of van der Waals heterostructures
Authors: Qi Junlei , Wu Zongxiao , Wang Wenbin , Bao Kai , Wang Lingzhi , Wu Jingkun , Ke Chengxuan , Xu Yue , He Qiyuan
Published: March 2023

Highlights

The major synthetic strategies of van der Waals heterostructures based on 2D materials are introduced, including physical combination, gas-phase deposition, solvothermal synthesis and synchronous evolution.

The fundamental principles, development trends, and strengths/weaknesses of each synthetic strategy are elaborated.

The integration strategies of van der Waals heterostructures and their preferred applications are discussed, including electronics, photodetectors and energy-related applications.

The potentials and challenges arising in the van der Waals heterostructures synthesis and applications are envisioned.
Neumann boundary value problems for elliptic operators with measure-valued coefficients
Authors: Wei Rong , Yang Saisai , Zhang Tusheng
Published: March 2023

In this paper, we prove that there exists a unique weak solution to the Neumann boundary value problem for second order elliptic operators whose coefficients are signed measures. We will give a probabilistic representation of the solution. The heat kernel estimates and reflected diffusion processes play important roles.
On the role of myosin-induced actin depolymerization during cell migration
Authors: Yao Lingxing , Mori Yoichiro , Sun Sean X. , Li Yizeng
Published: March 2023

This work quantified how cell velocity and effective power output are influenced by the rate of actin depolymerization, which is affected by myosin contraction. Model analysis shows that the cell migration velocity displays a biphasic dependence on the rate of actin depolymerization and myosin contraction.
Offering No-Cost Cosmetic Revisions: The Experience of an Academic Cosmetic Surgery Program
Authors: Moura Steven P , Wirth Peter J , Shaffrey Ellen C , Attaluri Pradeep K , Rao Venkat K
Published: March 2023

Background

The financial principles of a no-cost revision policy and their implications for revision rates are not well understood.

Objectives

Therefore, the primary objective of this retrospective study is to report our no-cost revision rates and, secondarily, to survey the cosmetic revision policies of other cosmetic surgery practices and detail the financial principles underpinning no-cost revisions.

Methods

All aesthetic surgeries and no-cost revisions performed by the plastic surgeons, oculoplastic surgeons, and facial plastic and reconstructive surgeons at our academic outpatient cosmetic surgery center from January 1, 2016 to June 30, 2022 were identified using procedural codes. Data on the number of surgeries, number of revisions, operative minutes, and time intervals between initial and revision surgeries were collected. A survey was administered to assess the revision policies of similar cosmetic surgery practices.

Results

A total of 1491 aesthetic surgeries and minimally invasive procedures were included, and 125 revision procedures were performed (8.4%). Thigh lifts (3, 13.6%), rhinoplasties or septoplasties (25, 15.8%), and otoplasties (3, 27.3%) had the highest revision rates. Three practices (15%) offered cosmetic revisions at no cost, 9 (45%) did not apply a surgeon's fee, 5 (25%) evaluated fees on a case-by-case basis, 1 (5%) offered revisions with an insurance policy, and 2 (10%) cosmetic surgery practices did not offer revisions at a reduced rate.

Conclusions

Despite offering revisions at no cost, our revision rates are reasonable for an academic cosmetic surgery practice. The revision policies offered to patients on the private market are varied, but most surveyed practices offer revisions at either a reduced rate or no cost.

Level of Evidence: 4
Mutations in plasticity-related-gene-1 (PRG-1) protein contribute to hippocampal seizure susceptibility and modify epileptic phenotype
Authors: Knierim Ellen , Vogt Johannes , Kintscher Michael , Ponomarenko Alexey , Baumgart Jan , Beed Prateep , Korotkova Tatiana , Trimbuch Thorsten , Panzer Axel , Steinlein Ortrud K , Stephani Ulrich , Escayg Andrew , Koko Mahmoud , Liu Yuanyuan , Lerche Holger , Schmitz Dietmar , Nitsch Robert , Schuelke Markus
Published: March 2023

The Phospholipid Phosphatase Related 4 gene (PLPPR4,  *607813) encodes the Plasticity-Related-Gene-1 (PRG-1) protein. This cerebral synaptic transmembrane-protein modulates cortical excitatory transmission on glutamatergic neurons. In mice, homozygous Prg-1 deficiency causes juvenile epilepsy. Its epileptogenic potential in humans was unknown. Thus, we screened 18 patients with infantile epileptic spasms syndrome (IESS) and 98 patients with benign familial neonatal/infantile seizures (BFNS/BFIS) for the presence of PLPPR4 variants. A girl with IESS had inherited a PLPPR4-mutation (c.896C > G, NM_014839; p.T299S) from her father and an SCN1A-mutation from her mother (c.1622A > G, NM_006920; p.N541S). The PLPPR4-mutation was located in the third extracellular lysophosphatidic acid-interacting domain and in-utero electroporation (IUE) of the Prg-1p.T300S construct into neurons of Prg-1 knockout embryos demonstrated its inability to rescue the electrophysiological knockout phenotype. Electrophysiology on the recombinant SCN1Ap.N541S channel revealed partial loss-of-function. Another PLPPR4 variant (c.1034C > G, NM_014839; p.R345T) that was shown to result in a loss-of-function aggravated a BFNS/BFIS phenotype and also failed to suppress glutamatergic neurotransmission after IUE.

The aggravating effect of Plppr4-haploinsufficiency on epileptogenesis was further verified using the kainate-model of epilepsy: double heterozygous Plppr4−/+|Scn1awt|p.R1648H mice exhibited higher seizure susceptibility than either wild-type, Plppr4-/+, or Scn1awt|p.R1648H littermates. Our study shows that a heterozygous PLPPR4 loss-of-function mutation may have a modifying effect on BFNS/BFIS and on SCN1A-related epilepsy in mice and humans.
Machine learning classifiers for electrode selection in the design of closed-loop neuromodulation devices for episodic memory improvement
Authors: Wang David X , Ng Nicole , Seger Sarah E , Ekstrom Arne D , Kriegel Jennifer L , Lega Bradley C
Published: March 2023

Successful neuromodulation approaches to alter episodic memory require closed-loop stimulation predicated on the effective classification of brain states. The practical implementation of such strategies requires prior decisions regarding electrode implantation locations. Using a data-driven approach, we employ support vector machine (SVM) classifiers to identify high-yield brain targets on a large data set of 75 human intracranial electroencephalogram subjects performing the free recall (FR) task. Further, we address whether the conserved brain regions provide effective classification in an alternate (associative) memory paradigm along with FR, as well as testing unsupervised classification methods that may be a useful adjunct to clinical device implementation. Finally, we use random forest models to classify functional brain states, differentiating encoding versus retrieval versus non-memory behavior such as rest and mathematical processing. We then test how regions that exhibit good classification for the likelihood of recall success in the SVM models overlap with regions that differentiate functional brain states in the random forest models. Finally, we lay out how these data may be used in the design of neuromodulation devices.
Converting an infant with borderline left heart structures to biventricular circulation after an initial hybrid Norwood approach: a case report
Authors: Cassanello Pia , Andreas Eicken , Maria Von Stumm , Stanimir Georgiev
Published: March 2023

Background

Hybrid approach in hypoplastic left heart syndrome (HLHS) implies placement of bilateral pulmonary artery bands and ductal stenting. This approach serves as a less invasive surgical–interventional alternative to the Norwood procedure with reported equivalent survival. Potential benefits include deferrable surgical risks and in some borderline left ventricle patients, when combined with a restrictive inter-atrial communication, it offers a chance for biventricular circulation.

Case summary

Term newborn with total anomalous pulmonary venous connection (TAPVC), hypoplastic left heart, small aortic arch, and atrial septal defect (ASD) who was multi-disciplinary deemed eligible for a hybrid palliation performed on day six of life after TAPVC surgical correction. Subsequently, percutaneous ductal stent implantation was performed (two Sinus Superflex-DS stents) on day 11 of life. Magnetic resonance imaging (MRI) showed a hypoplastic non-apex-forming left ventricle (LV) [left ventricular end-diastolic volume index (LVEDVI) 15 mL/m2]. On day 27th of life, the ASD was closed surgically with a fenestrated patch. At 2 months of age, control cardiac MRI showed striking LV growth (LVEDVI 37 mL/m2). Herein an interventional hybrid take-down was performed with dilatation of both pulmonary arterial bands and closure of the ductal stent with an Amplatzer Vascular plug II, thus achieving biventricular circulation.

Discussion

Hybrid approach has proven as a safe alternative to the Norwood procedure for HLHS. This case illustrates the importance of multi-disciplinary care in high-risk two ventricular patients by means of LV rehabilitation. Further studies are needed to systematically define and understand the intricacies of potential candidates for staged biventricular repair initially managed with hybrid approach.
Sustainable goal-oriented smart environments: a declarative programming approach
Authors: Bisicchia Giuseppe , Forti Stefano , Brogi Antonio
Published: March 2023

The sustainable management of smart environments enabled by the Internet of Things (IoT) requires new methodologies and tools to suitably handle potentially many users and their objectives on cyber-physical systems, e.g. smart lighting, smart A/C. In this article, we propose a declarative framework to model IoT-enabled smart environments. Our methodology permits (i) expressing user roles and hierarchical environments, (ii) declaring customized policies to mediate user objectives into a target state and (iii) determining valid settings for IoT actuators to achieve such a target also reducing energy consumption. An open-source Prolog prototype of the framework is showcased over two lifelike motivating examples and its scalability is assessed at increasing sizes of the managed smart environment.
Contributions of the Department of Defense Congressionally Directed Medical Research Programs to Advances in Cancer Therapeutics
Authors: Neagley Melanie , Helsel Alexis , Buachie Regina , Behrsing Tracy , Ghosh Sagar , Vaday Gayle , Cunningham Melissa D
Published: March 2023

Nearly a billion dollars is spent annually in the Military Health System (MHS) on cancer diagnosis and treatment, with a large portion of that directed toward breast, prostate, and ovarian cancers. Multiple studies have demonstrated the impact of specific cancers on MHS beneficiaries and Veterans, highlighting the fact that active duty and retired military members have a higher incidence than the general public for many chronic diseases and certain forms of cancer. The Congressionally Directed Medical Research Programs have supported research that has contributed to the development, clinical testing, and commercialization of 11 cancer drugs approved by the Food and Drug Administration to treat breast, prostate, or ovarian cancers. In addition to hallmark funding mechanisms that prioritize innovative, groundbreaking ideas, the Congressionally Directed Medical Research Program’s cancer programs continue to identify new approaches to fill critical gaps across the full research spectrum, including bridging the translational research gap toward developing new treatments for cancer patients in the MHS and in the general American public.
Thermal emission from the hot Jupiter WASP-103 b in J and Ks bands
Authors: Shi Yaqing , Wang Wei , Zhao Gang , Zhai Meng , Chen Guo , Jiang Zewen , Ouyang Qinglin , Henning Thomas , Zhao Jingkun , Crouzet Nicolas , van Boekel Roy , Esteves Lisa
Published: March 2023

Hot Jupiters, particularly those with temperature higher than 2000 K, are the best sample of planets that allow in-depth characterization of their atmospheres. We present here a thermal emission study of the ultrahot Jupiter WASP-103 b observed in two secondary eclipses with CFHT/WIRCam in J and Ks bands. By means of high precision differential photometry, we determine eclipse depths in J and Ks to an accuracy of 220 and 270 ppm, which are combined with the published HST/WFC3 and Spitzer data to retrieve a joint constraints on the properties of WASP-103 b dayside atmosphere. We find that the atmosphere is best fit with a thermal inversion layer included. The equilibrium chemistry retrieval indicates an enhanced C/O (1.35$^{+0.14}_{-0.17}$) and a supermetallicity with [Fe/H]$=2.19^{+0.51}_{-0.63}$ composition. Given the near-solar metallicity of WASP-103 of [Fe/H] = 0.06, this planet seems to be ∼100 more abundant than its host star. The free chemistry retrieval analysis yields a large abundance of FeH, H−, CO2, and CH4. Additional data of better accuracy from future observations of JWST should provide better constraint of the atmospheric properties of WASP-103b.
Chaotic winds from a dying world: a one-dimensional map for evolving atmospheres
Authors: Bromley Joshua , Chiang Eugene
Published: March 2023

Planets that are smaller than Mercury and heated to sublimation temperatures of ∼2000 K lose mass catastrophically in dusty evaporative winds. The winds are observed to gust and recede largely without pattern; transit depths from the Kepler mission vary randomly from orbit to orbit by up to a factor of 10 or more. We explain how chaotic outflows may arise by constructing a map for the wind mass-loss rate as a function of time. The map is built on three statements: (1) The wind mass-loss rate scales in proportion to the surface equilibrium vapour pressure, rising exponentially with ground temperature. (2) Because the wind takes a finite time to escape the planet’s gravity well, the surface mass-loss rate at any time determines the wind optical depth at a later time—the atmosphere has hysteresis. (3) The ground temperature increases with optical depth (greenhouse effect) when the atmosphere is optically thin and decreases with optical depth when the atmosphere is optically thick (nuclear winter). Statement (3) follows from how dust condenses in the face of intense stellar irradiation. As discussed recently, condensates initially naked before the star must be silicate-rich and iron-poor, staying cool enough for condensation by absorbing weakly in the visible and emitting strongly in the infrared. Later, when grains are numerous enough to self-shield from starlight, they may accrete more iron and reverse their visible-to-infrared opacity ratio. Depending on parameters, the map for the wind can regularly boom and bust between a greenhouse and a nuclear winter, or erupt into chaos. Lyapunov times are measured in orbital periods, the time for the wind to turn by Coriolis forces away from the planet’s dayside, out of the Hill sphere.
Flap endonuclease Rad27 cleaves the RNA of R-loop structures to suppress telomere recombination
Authors: Liu Chia-Chun , Chan Hsin-Ru , Su Guan-Chin , Hsieh Yan-Zhu , Lei Kai-Hang , Kato Tomoka , Yu Tai-Yuan , Kao Yu-wen , Cheng Tzu-Hao , Chi Peter , Lin Jing-Jer
Published: March 2023

The long non-coding telomeric RNA transcript TERRA, in the form of an RNA–DNA duplex, regulates telomere recombination. In a screen for nucleases that affects telomere recombination, mutations in DNA2, EXO1, MRE11 and SAE2 cause severe delay in type II survivor formation, indicating that type II telomere recombination is mediated through a mechanism similar to repairing double-strand breaks. On the other hand, mutation in RAD27 results in early formation of type II recombination, suggesting that RAD27 acts as a negative regulator in telomere recombination. RAD27 encodes a flap endonuclease that plays a role in DNA metabolism, including replication, repair and recombination. We demonstrate that Rad27 suppresses the accumulation of the TERRA-associated R-loop and selectively cleaves TERRA of R-loop and double-flapped structures in vitro. Moreover, we show that Rad27 negatively regulates single-stranded C-rich telomeric DNA circles (C-circles) in telomerase-deficient cells, revealing a close correlation between R-loop and C-circles during telomere recombination. These results demonstrate that Rad27 participates in telomere recombination by cleaving TERRA in the context of an R-loop or flapped RNA–DNA duplex, providing mechanistic insight into how Rad27 maintains chromosome stability by restricting the accumulation of the R-loop structure within the genome.
Rust Disease Caused by Uredinopsis osmundae on Balsam Fir, Canaan Fir, White Fir, and Sensitive Fern Reported from Pennsylvania, United States
Authors: Gómez-Zapata Paula A. , Davis Donald D. , Aime Mary Catherine
Published: March 2023

Pennsylvania is the fourth-largest Christmas-tree-producing state in the United States, with annual sales of more than $22 million. During the summers of 2018 and 2019, a rust disease was observed on the leaves of balsam fir, Canaan fir, white fir, and sensitive fern in a Christmas tree crop in Pennsylvania. The specimens were sent to the Arthur Fungarium at Purdue University for further identification and long-term deposit. Based on morphological characteristics and sequence analysis, the rust species was identified as Uredinopsis osmundae. To our knowledge, this is the first report of U. osmundae on balsam fir, Canaan fir, white fir, and sensitive fern in Pennsylvania.
Role of Terlipressin in Patients With Hepatorenal Syndrome-Acute Kidney Injury Admitted to the ICU: A Substudy of the CONFIRM Trial
Authors: Karvellas Constantine J. , Subramanian Ram , Olson Jody C. , Jamil Khurram
Published: March 2023

IMPORTANCE AND OBJECTIVES:

This study assessed the potential advantages of treating hepatorenal syndrome-acute kidney injury (HRS-AKI) with terlipressin versus placebo in the ICU setting.

DESIGN:

Patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days.

SETTING:

A retrospective analysis of data from the phase III CONFIRM study.

PARTICIPANTS:

Adult patients with HRS-AKI admitted to the ICU.

MAIN OUTCOMES AND MEASURES:

In this substudy, we evaluated outcomes of the ICU stay and the need for organ support, including renal replacement therapy (RRT).

RESULTS:

Among 300 patients with HRS-AKI from the CONFIRM study, 45 were treated in the ICU (terlipressin, 31/199 [16%]; placebo, 14/101 [14%]). On ICU admission, baseline demographics were similar across treatment arms, including severity of liver dysfunction. Among patients alive at the end of the ICU stay, those randomized to terlipressin had a significantly shorter median length of ICU stay than placebo (4 vs 11 d; p < 0.001). Terlipressin-treated patients had a significantly larger improvement in renal function from baseline versus placebo (–0.7 vs +0.2 mg/dL; p = 0.001), including when accounting for the interaction between treatment and day-of-patient-admission to the ICU (–0.7 vs +0.9 mg/dL; p < 0.001). Cumulative requirement for RRT through day 90 was improved in the terlipressin arm versus placebo (10/31 [32%] vs 8/14 [57%]; p = 0.12), although not significantly. Of 13 patients who received a liver transplant, five out of five (100%) in the placebo arm needed RRT through day 90 versus five out of eight (63%) in the terlipressin arm.

CONCLUSIONS:

In this subanalysis of CONFIRM, patients admitted to the ICU with HRS-AKI who received terlipressin were more likely to achieve renal function improvement, based on serum creatinine changes by the end of treatment, and had significantly shorter lengths of ICU stay than patients randomized to the placebo arm.
Internal Jugular Vein Cannulation in Prone Position
Authors: Salvador-Ibarra Ibzan J.
Published: March 2023

Since 1970, prone decubitus (PD) has been used as adjuvant therapy to treat severe hypoxia in patients with acute respiratory distress syndrome (ARDS), and now with the COVID-19 pandemic, its use has become widespread in ICUs. ARDS is characterized by diffuse bilateral radiographic infiltrates, decreased respiratory compliance, small lung volumes, and severe hypoxemia. The placement of vascular access in PD seems to be feasible and safe, since, as has been described, the number of complications such as pneumothorax, bleeding, and arterial punctures are almost nil, especially when performed under ultrasound guidance. The patients who could benefit most from this procedure seem to be those with obesity, mainly with a body mass index greater than 30 kg/m2, in whom the return to the supine position may represent a risk of respiratory or hemodynamic deterioration.
Quality of Life and Family Impact in Down Syndrome, Autism Spectrum Disorder, and Co-occurring Down Syndrome and Autism Spectrum Disorder
Authors: Soccorso Cara , Milliken Anna , Hojlo Margaret , Pawlowski Katherine , Weas Sarah , Sideridis Georgios , Baumer Nicole
Published: March 2023

Objective:

Families of children with neurodevelopmental disorders have developmental, behavioral, and social-emotional needs that affect quality of life (QoL). This study assesses the validity and utility of a caregiver QoL measure; characterizes QoL in families with children with Down syndrome (DS), autism spectrum disorder (ASD), and a dual diagnosis of DS and ASD (DS + ASD); and compares and explores differences in QoL based on diagnosis.

Methods:

Caregivers of children and adolescents with ASD (n = 610) and DS (n = 177) completed the Pediatric Quality of Life Inventory Family Impact Module 2.0, yielding overall, parent functioning, family functioning, and subscale scores, and a Parent Global Impression (PGI) rating. An ASD cohort (n = 177) was sex matched to the DS cohort (n = 177) to mitigate potential sex bias. Additional analyses compared these groups with children and adolescents with DS + ASD (n = 37).

Results:

Analyses showed that the Pediatric Quality of Life Inventory was valid and reliable in DS, ASD, and DS + ASD populations. No differences were reported in PGI ratings among groups. Caregivers in the DS group demonstrated higher QoL and family functioning compared with the ASD and DS + ASD groups. The DS group reported significantly better Emotional Functioning and Communication and less Worry than the ASD group. Compared with the ASD group, caregivers of the DS + ASD group indicated more concerns with Physical Functioning. Notably, the DS + ASD group had significantly lower levels of QoL than the DS group in nearly all caregiver functioning domains.

Conclusion:

This study highlights differences in QoL within and between neurodevelopmental disorder groups, which may help identify families requiring additional support, advocacy, and community engagement.
Combining Proximal Foam Sclerotherapy and Distal Endovenous Laser Ablation for Recurrent Varicose Vein Treatment
Authors: Bossart Simon , Kos Sebastian , Keo Hak Hong , Staub Daniel , Uthoff Heiko
Published: March 2023

BACKGROUND

Recurrent varicose veins with neovascularization are a common clinical problem. Although endovenous laser ablation (EVLA) has become the standard treatment modality to treat truncal veins, additional sclerotherapy is required to treat newly formed tortuous veins. A novel laser fiber with an injection channel (nLF) allows for such simultaneous proximal sclerotherapy and offers a potentially more effective treatment option.

OBJECTIVE

The aim of this study was to present our experience using the nLF for combined EVLA and sclerotherapy treatment of symptomatic recurrent varicose veins.

MATERIALS AND METHODS

A retrospective single-center cohort study analyzed the outcomes of all patients with symptomatic recurrent varicose veins, treated with an nLF between September 2020 and August 2022.

RESULTS

In total, 28 combined EVLA/sclerotherapy procedures performed with the nLF in 26 patients were analyzed. In all cases, neovascularizations were treated by sclerotherapy through the nLF catheter, followed by laser ablation of the remaining truncal veins. All follow-up ultrasound examinations showed persistent complete occlusion of the treated truncal veins and neovascularizations. No clinically relevant complications were observed.

CONCLUSION

Combining proximal foam sclerotherapy and distal EVLA using an nLF for the treatment of symptomatic recurrent varicose veins is safe and effective.
How the Science of Radiation Biology Can Help Reduce the Crippling Fear of Low-level Radiation
Authors: Brooks Antone L. , Conca James , Glines Wayne M. , Waltar Alan E.
Published: March 2023

The fear of radiation has been present almost since the discovery of radiation, but has intensified since the “dawn of the atomic age” over 75 y ago. This fear has often served as an impediment to the safe and beneficial uses of radiation and radioactive material. The underlying causes of such fear are varied, can be complex, and are often not associated with any scientific knowledge or understanding. The authors believe that a clear understanding of the current scientific knowledge and understanding of the effects of radiation exposure may be useful in helping to allay some of the fear of radiation. This manuscript attempts to (1) address several scientific questions that we believe have contributed to the fear of radiation, (2) review the data derived from research that can be used to address these questions, and (3) summarize how the results of such scientific research can be used to help address the fear of low-dose and low-dose-rate radiation. Several examples of how fear of radiation has affected public perception of radiological events are discussed, as well as a brief history of the etiology of radiation fear. Actions needed to reduce the public fear of radiation and help fulfill the full societal benefits of radiation and radioactive materials are suggested.
EXACERBATED TOURETTE SYNDROME DIAGNOSED IN ADULTHOOD AFTER RECURRENT BILATERAL RETINAL DETACHMENT
Authors: Mito Tsuyoshi , Okemoto Hajime , Kawasaki Akane , Sasaki Hiroshi
Published: March 2023

Purpose:

The purpose of this study was to report a case of Tourette syndrome, exacerbated in adulthood, that was diagnosed after bilateral lens luxation and recurrent retinal detachment due to self-injury.

Methods:

This was a case report.

Results:

A 35-year-old man presented with a sudden abnormality in vision and bilateral lens luxation. The patient successfully underwent bilateral lens extraction and intrascleral intraocular lens fixation; however, vitreous hemorrhage and retinal detachment occurred in the left eye. The retinal detachment was caused by a giant retinal tear and retinal dialysis. Vitrectomy was performed. However, retinal detachment recurred with proliferative vitreoretinopathy. Retinal detachment subsequently occurred in the right eye. Self-injury to the eye was observed before surgical treatment. The patient was consequently diagnosed with Tourette syndrome.

Conclusion:

Tourette syndrome, which may be accompanied by self-injurious behavior, is a disorder that typically develops in childhood but rarely exacerbates during adulthood. A diagnosis of Tourette syndrome should be considered in cases of unexplained retinal detachment with traumatic features.
Refractory severe idiopathic thrombocytopenia and treatment challenges
Authors: Shahnazi Anahita , Johnston Brandon , Hargrove Mark , Patolia Harsukh , Junko Gretchen
Published: March 2023

Introduction:

Refractory idiopathic thrombocytopenia (ITP) is a disease that does not respond to or relapses after splenectomy, requires treatment to reduce the risk of clinically significant bleeding, and is a challenging case to treat.

Presentation of the Case:

A 39-year-old male with a history of chronic ITP presented with a platelet count of 1000/µl and prostatitis. He was started on Ciprofloxacin and started intravenous immunoglobulin along with intravenous methylprednisolone. Then Rituximab was started on day fourth. Since his platelet remained 0/µl, Mycophenolate mofetil (Cellcept) was started on day 14th. Next, a dose of Romiplostim on day 19th was given. Eltrombopag (Promacta) and Tavlesse were started on day 23th and platelets rose to 96×103/µl on day 26th and then 418×103/µl.

Discussion:

Normally, refractory ITP patients who do not respond to first-line treatments require a combination therapy of one to two medicines of the second line, like thrombopoietin receptor agonists. However, this patient’s thrombocytopenia neither responded to first-line treatment nor second-line treatment with Promacta/Romiplostin plus immunosuppressives or Tavlesse.

Conclusion:

Refractory ITP, who has not responded to first-line and second-line treatments, requires treatment with a combination of all first-line and second-line treatments. Furthermore, Promacta, Tavlesse, and Romiplostim have a big role to play in helping the patient.
“Diagnostic Accuracy of Two Manual Muscle Testing Scales for Identifying Upper Extremity Nerve Transfer Candidates in Children with Acute Flaccid Myelitis”
Authors: Werner Julie M. , Wlodarczyk Jordan , Seruya Mitchel
Published: March 2023

Background:

Manual muscle testing is a mainstay of strength assessment despite not having been compared to intraoperative electrical stimulation of peripheral nerves.

Methods:

Intraoperative electrical stimulation served as the reference standard in evaluating predictive accuracy of the Active Movement Scale (AMS) and the Medical Research Council (MRC) scale. Retrospective consecutive sampling of all patients with AFM who underwent exploration or nerve transfer at a pediatric multidisciplinary brachial plexus and peripheral nerve center March 2016 - July 2020 were included. The nonparametric area under the curve (AUC) was calculated. Optimal cutoff score (Youden’s J) and diagnostic accuracy values were reported. AMS and MRC were directly compared for predictive superiority.

Results:

181 upper extremity nerves (73 donor nerve candidates, 108 recipient nerve candidates) were tested intraoperatively from 40 children (mean age 7.9 years, SD: 4.9). The scales performed similarly (p=.953) in classifying suitable donor nerves with satisfactory accuracy (AUCAMS: 71.5%, AUCMRC: 70.7%; optimal cutoff: AMS >5, MRC >2). The scales performed similarly (p=.688) in classifying suitable recipient nerves with good accuracy (AUCAMS: 92.1%, AUCMRC: 94.9%; optimal cutoff: AMS ≤3, MRC ≤1).

Conclusions:

Manual muscle testing is an accurate, non-invasive means of identifying donor and recipient nerves for transfer in children with acute flaccid myelitis. The utility of these results is in minimizing unexpected findings in the operating room and aiding in the development of contingency plans. Further research may extend these findings to test the validity manual muscle testing as outcome measures of the success of nerve transfer.
Controlling Supratip Break and Tip Rotation and Projection with Preservation of Pitanguy’s Ligament
Authors: Öztürk Güncel
Published: March 2023

In the present study, the author describes a new closed rhinoplasty technique in which Pitanguy’s ligament was protected, ultimately resulting in better supratip break, tip projection and tip rotation. Based on the inclusion and exclusion criteria, the records of 156 patients who underwent surgery with this “Pitanguy’s Ligament Protection and Suturing” technique were evaluated retrospectively. In this novel technique, Pitanguy’s ligament was dissected from the proximal and distal points with scissors in the lower third, and it was left intact. There was no need for revision operations in any patient. Twelve months after surgery, the ROE scores ranged between 80 and 100 points. The median score was 86.5 points. Patient satisfaction was excellent in 90% of the included cases. Protection of Pitanguy’s ligament and attachment of this ligament to the nasal tip create better tip definition and generate several aesthetic and functional advantages.
Assessing how Age, Sex, Race, and Education Affect the Relationships Between Cognitive Domains and Odor Identification
Authors: Zhong Selena , Wroblewski Kristen E. , Laumann Edward O. , McClintock Martha K. , Pinto Jayant M.
Published: March 2023

Background:

The associations between cognitive domains and odor identification are well established, but how sociodemographic variables affect these relationships is less clear.

Purpose:

Using the survey-adapted Montreal Cognitive Assessment instrument (MoCA-SA), we assess how age, sex, race, and education shape these relationships.

Methods:

We first used cluster analysis and multidimensional scaling to empirically derive distinct cognitive domains from the MoCA-SA as it is unclear whether the MoCA-SA can be disaggregated into cognitive domains. We then used ordinal logistic regression to test whether these empirically derived cognitive domains were associated with odor identification and how sociodemographic variables modified these relationships.

Study Population:

Nationally representative sample of community-dwelling US older adults.

Results:

We identified 5 out of the 6 theoretical cognitive domains, with the language domain unable to be identified. Odor identification was associated with episodic memory, visuospatial ability, and executive function. Stratified analyses by sociodemographic variables reveal that the associations between some of the cognitive domains and odor identification varied by age, sex, or race, but not by education.

Conclusions:

These results suggest that (1) the MoCA-SA can be used to identify cognitive domains in survey research and (2) the performance of smell tests as a screener for cognitive decline may potentially be weaker in certain subpopulations.
Androgen-armoured amazons: reversed sex roles in coucals are associated with testosterone in females but not males
Authors: Goymann Wolfgang
Published: March 2023

In some species, sexual selection is stronger in females than males. In classically polyandrous birds, for instance, females compete for mating opportunities and males care for offspring. Sex steroids such as testosterone have been suggested to regulate the behaviours of ‘role-reversed’ females and males, but comparative studies did not find evidence for a role of testosterone in relation to sex roles. However, the large variability of hormone measurements across laboratories may prevent detecting subtle differences in hormone levels. To circumvent this caveat, I compared sex steroid concentrations of females and males of two closely related and cohabiting species with different mating systems: the classically polyandrous black coucal (
Centropus grillii
) and the monogamous white-browed coucal (
C. superciliosus
). Baseline and gonadotropin-releasing hormone (GnRH)-induced testosterone concentrations were twice as high in female black coucals than female white-browed coucals, and the low pre-breeding progesterone concentrations of female black coucals were consistent with progesterone's modulatory role during agonistic interactions in this species. Baseline and GnRH-induced testosterone and progesterone concentrations did not differ between males of both species. This study provides first evidence that elevated testosterone is associated with sex-role-reversed traits in females, whereas low levels of testosterone may not be necessary to facilitate sex-role reversal in males.
Cambrian ‘sap-sucking’ molluscan radulae among small carbonaceous fossils (SCFs)
Authors: Slater Ben J.
Published: March 2023

Molluscs have produced an extensive fossil record, owing to the prevalence of robust biomineralized shells among this clade. By contrast, most other components of molluscan anatomy are seldom preserved. Importantly, little is known of the evolutionary history of the unique molluscan feeding apparatus—the radula. A scarcity of fossil radulae has hampered our understanding of the ancestral condition, and of the dietary ecology of early molluscs. The handful of known fossil radulae all point to early molluscs as simple deposit feeders that obtained food via rasping or scraping. This study reports microscopic radulae preserved as ‘small carbonaceous fossils' (SCFs) from Cambrian (Stage 4–Wuliuan, approximately 514–504.5 Ma) strata of Sweden. These rare fossil radulae offer novel insights into the feeding anatomy and ecology of early molluscs. Each radula comprises a uniseriate arc of (≤10) blade-shaped teeth, fringed by a slicing keel. This distinctive morphology is strikingly convergent with the radulae of extant sacoglossan heterobranch gastropods—such radulae are specially adapted for piercing the cell walls of green algal tissues to enable suctorial feeding on the cytoplasm contents. Discovery of analogous Cambrian radulae demonstrates this specialized form of herbivory had already evolved among molluscs more than half a billion years ago.
Increased bacterial taxonomic and functional diversity is associated with impaired rotavirus vaccine immunogenicity in infants from India and Malawi
Authors: Cunningham-Oakes Edward , Bronowski Christina , Chinyama End , Jere Khuzwayo C. , Sindhu Kulandaipalayam Natarajan C. , Kang Gagandeep , Iturriza-Gómara Miren , Darby Alistair C. , Parker Edward P. K.
Published: March 2023

The immunogenicity and effectiveness of oral rotavirus vaccines (ORVs) against severe rotavirus-associated gastroenteritis is impaired in low- and middle-income countries (LMICs) where the burden of disease is highest. Determining risk factors for impaired ORV response may help identify strategies to enhance vaccine effectiveness. In this study, we use metagenomic sequencing to provide a high-resolution taxonomic analysis of stool samples collected at 6 weeks of age (coinciding with the first ORV dose) during a prospective study of ORV immunogenicity in India and Malawi. We then analyse the functional capacity of the developing microbiome in these cohorts. Microbiome composition differed significantly between countries, although functional capacity was more similar than taxonomic composition. Our results confirm previously reported findings that the developing microbiome is more diverse in taxonomic composition in ORV non-seroconverters compared with seroconverters, and we additionally demonstrate a similar pattern in functional capacity. Although taxonomic or functional feature abundances are poor predictors of ORV response, we show that skews in the direction of associations within these microbiome data can be used to identify consistent markers of ORV response across LMIC infant cohorts. We also highlight the systemic under-representation of reference genes from LMICs that limit functional annotation in our study (7% and 13% annotation at pathway and enzyme commission level, respectively). Overall, higher microbiome diversity in early life may act as marker for impaired ORV response in India and Malawi, whilst a holistic perspective of functional capacity may be hidden in the “dark matter” of the microbiome.
A prescriptive optimization approach to identification of minimal barriers for surgical patients
Authors: Khaniyev Taghi , Copenhaver Martin S. , Safavi Kyan C. , Zenteno Langle Ana Cecilia , Starobinski Keren S. , Daily Bethany , Dunn Peter , Levi Retsef
Published: March 2023

Problem definition

Ensuring timely patient discharges is central to managing a hospital’s patient flow; however, discharges are dependent on the coordination of multiple care teams and thus are highly decentralized in nature. Therefore, central capacity teams often lack transparency into how to prioritize scarce resources (e.g., imaging, post-hospital facility placement) for patients who need them for timely discharge. Our goal is to identify a small subset of such barriers for hospitalized surgical patients by balancing two aims: a high likelihood that the patient will be discharged from the hospital in the next 24 hours if these barriers are resolved; and a high likelihood that these barriers will indeed be resolved.

Methodology/results

We leverage a machine learning model that predicts the likelihood of a patient’s discharge in the next 24 hours and train another set of machine learning models that predict, for each open barrier of a patient, the likelihood that the barrier will be resolved prior to discharge. We then combine these predictive models with a mixed-integer prescriptive optimization model to identify a subset of issues called minimal barriers. We empirically demonstrate the efficacy of the proposed formulation and solution methodology in identifying a small number of minimal barriers using real data from a large academic medical center. We also study the influence of variability in discharge prediction estimates on the prescribed barriers; we introduce a robust optimization variant which incorporates this directly, and we demonstrate that this is capable of overcoming several shortcomings of the nominal approach.

Managerial implications

The modeling framework we propose can significantly enhance the ability of capacity management teams to identify significant barriers to care progression and understand which barriers are most important to address (based on their relationship with patient discharge) while taking into account the heterogeneity of barriers and their resolution.
Methamphetamine (MA) use, MA dependence, and MA-induced psychosis are associated with increasing aberrations in the compensatory immunoregulatory system and interleukin-1α and CCL5 levels
Authors: Kalayasiri Rasmon , Dadwat Kanokwan , Thika Supaksorn , Sirivichayakul Sunee , Maes Michael
Published: March 2023

Comprehensive immunological profiles have not been studied in relation to methamphetamine (MA) use, MA dependency, or MA-induced psychosis (MAP). Using the BioPlex Pro Human Cytokine 48-Plex panel, this study measured M1 macrophage, T helper (Th)-1, Th-2, growth factor, and chemokine profiles, as well as the immune inflammatory response system (IRS) and compensatory immunoregulatory system (CIRS) in peripheral blood samples from patients with MA use (n=51), MA dependence (n=47), and MAP (n=43) in comparison with healthy controls (n=43). We discovered that persistent MA use had a robust dose-dependent suppressive impact on all immunological profiles, suggesting extensive immunosuppression. The most reliable biomarker profile of MA use is the combination of substantial CIRS suppression and a rise in selected pro-inflammatory cytokines, namely CCL27 (CTACK), CCL11 (eotaxin), and interleukin (IL)-1α. In addition, MA dependency is related with a more severe immunosuppression, as demonstrated by lower stem cell factor and higher IL-10 levels. MAP is related with a significant decrease in all immunological profiles, particularly CIRS, and an increase in CCL5 (RANTES), IL-1α, and IL-12p70 signaling. In conclusion, long-term MA use and dependency severely undermine immune homeostasis. This results in widespread immunosuppression, which may increase the likelihood of infectious and immune illness or exacerbate disorders such as hepatitis and AIDS. Elevated levels of CCL5, CCL11, CCL27, IL-1α, and/or IL-12p70 may be associated with severe peripheral (atherosclerosis, cutaneous inflammation, immune aberrations, hypospermatogenesis) and central (neuroinflammation, neurotoxic, neurodegenerative, depression, anxiety and psychosis) side effects. Our message: “cease using MA, or better yet, never begin using MA”.