bluuebunny/crossref_metadata_2025 huggingface dataset:
On cohomological dimension of homomorphisms
Authors: De Saha Aditya , Dranishnikov Alexander
Published: June 2024

The (co)homological dimension of a homomorphism

ϕ
:
G
→
H

\phi :G\to H

is the maximal number

k
k

such that the induced homomorphism in

k
k

-th (co)homology groups is nonzero for coefficients in some

H
H

-module. It is known that for geometrically finite groups

G
,
c
d
(
G
)
=
h
d
(
G
)

G, cd(G)=hd(G)

and

c
d
(
G
×
G
)
=
2
c
d
(
G
)

cd(G\times G)=2cd(G)

. We prove analogous theorems for homomorphisms of geometrically finite groups.

The analogy stops working on the Eilenberg-Ganea equality

c
d
(
G
)
=
g
d
(
G
)

cd(G)=gd(G)

where

c
d
(
G
)
>
2

cd(G)>2

and

g
d
(
G
)

gd(G)

is the geometric dimension of

G
G

. We show that for every

k
>
2

k>2

there is a group homomorphism

ϕ
k

:

π
k

→

Z

k

\phi _k:\pi _k\to \mathbb {Z}^k

with

c
d
(

ϕ
k

)
>
k

cd(\phi _k)>k

and

g
d
(

ϕ
k

)
=
k

gd(\phi _k)=k

where

π
k

\pi _k

is the fundamental group of a closed aspherical

(
k
+
1
)

(k+1)

-dimensional manifold.
A note on a theorem of Hausdorff
Authors: Pol Roman , Reńska Mirosława
Published: June 2024

We give a topological proof (using directly some known results about infinite-dimensional spaces) of the following strengthening of a remarkable Hausdorff theorem: each separable metrizable space admitting a continuous map onto

[
0
,
1
]

[0,1]

is the union of a sequence

G
1

⊂
…
⊂

G

ξ

⊂
…

G_1 \subset \ldots \subset G_{\xi } \subset \ldots

,

ξ

>

ω

1

{\xi } > {\omega }_1

,

G

ξ

≠
X

G_{\xi } \not = X

, of zero-dimensional

G

δ

G_{\delta }

-sets in

X
X

such that for any finite Borel measure

μ
\mu

on

X
X

,

μ
(
X
∖

G

ξ

)
=
0

\mu (X \setminus G_{\xi }) = 0

, for some

ξ

{\xi }

. Our approach yields also an analogous result in a more general setting of ccc

σ
\sigma

-ideals.

Proofs of the Hausdorff theorem in the literature are based on subtle combinatorial reasonings.
Mobile calculator application for estimating human erythrocyte antigen frequency in Korea
Authors: Shin Dong Woo , Hong Yun Ji , Park Kyoung Un
Published: June 2024

Objectives

This study aimed to establish a comprehensive human erythrocyte antigen (HEA) frequency data set for Koreans. It also sought to develop a mobile app that facilitates the calculation of the frequencies of specific antigen-negative red blood cell units and the average number of units required for antigen typing.

Methods

Human erythrocyte antigen frequencies were compiled from large-scale blood donor data and 5 previous papers. Based on the collected data, we developed a mobile calculator app for HEA frequency and evaluated its usability.

Results

Human erythrocyte antigen frequency data for 20 blood group systems, including the ABO, Rh, MNS, Duffy, Kidd, and Diego systems, were established. The app was designed to enable users to select the desired phenotype from a drop-down menu and display the calculated frequency at the bottom. The number of units required for antigen typing to find 1 compatible red blood cell unit was also displayed. Five users participated in app evaluation and rated the functionality and information categories highly. In quizzes prompting users to calculate frequencies using the app, all participants provided correct answers, confirming the app’s user-friendly functionality.

Conclusions

This app, which encompasses comprehensive HEA frequency data, is expected to find multiple uses in transfusion medicine, including optimizing blood bank workflow and defining rare blood groups in Korea.
A joint normal-ordinal (probit) model for ordinal and continuous longitudinal data
Authors: Delporte Margaux , Molenberghs Geert , Fieuws Steffen , Verbeke Geert
Published: June 2024

In biomedical studies, continuous and ordinal longitudinal variables are frequently encountered. In many of these studies it is of interest to estimate the effect of one of these longitudinal variables on the other. Time-dependent covariates have, however, several limitations; they can, for example, not be included when the data is not collected at fixed intervals. The issues can be circumvented by implementing joint models, where two or more longitudinal variables are treated as a response and modeled with a correlated random effect. Next, by conditioning on these response(s), we can study the effect of one or more longitudinal variables on another. We propose a normal-ordinal(probit) joint model. First, we derive closed-form formulas to estimate the model-based correlations between the responses on their original scale. In addition, we derive the marginal model, where the interpretation is no longer conditional on the random effects. As a consequence, we can make predictions for a subvector of one response conditional on the other response and potentially a subvector of the history of the response. Next, we extend the approach to a high-dimensional case with more than two ordinal and/or continuous longitudinal variables. The methodology is applied to a case study where, among others, a longitudinal ordinal response is predicted with a longitudinal continuous variable.
Subthalamic control of impulsive actions: insights from deep brain stimulation in Parkinson’s disease
Authors: Herz Damian M , Frank Michael J , Tan Huiling , Groppa Sergiu
Published: June 2024

Control of actions allows adaptive, goal-directed behaviour. The basal ganglia, including the subthalamic nucleus, are thought to play a central role in dynamically controlling actions through recurrent negative feedback loops with the cerebral cortex. Here, we summarize recent translational studies that used deep brain stimulation to record neural activity from and apply electrical stimulation to the subthalamic nucleus in people with Parkinson’s disease.

These studies have elucidated spatial, spectral and temporal features of the neural mechanisms underlying the controlled delay of actions in cortico-subthalamic networks and demonstrated their causal effects on behaviour in distinct processing windows. While these mechanisms have been conceptualized as control signals for suppressing impulsive response tendencies in conflict tasks and as decision threshold adjustments in value-based and perceptual decisions, we propose a common framework linking decision-making, cognition and movement. Within this framework, subthalamic deep brain stimulation can lead to suboptimal choices by reducing the time that patients take for deliberation before committing to an action. However, clinical studies have consistently shown that the occurrence of impulse control disorders is reduced, not increased, after subthalamic deep brain stimulation surgery. This apparent contradiction can be reconciled when recognizing the multifaceted nature of impulsivity, its underlying mechanisms and modulation by treatment. While subthalamic deep brain stimulation renders patients susceptible to making decisions without proper forethought, this can be disentangled from effects related to dopamine comprising sensitivity to benefits versus costs, reward delay aversion and learning from outcomes.

Alterations in these dopamine-mediated mechanisms are thought to underlie the development of impulse control disorders and can be relatively spared with reduced dopaminergic medication after subthalamic deep brain stimulation. Together, results from studies using deep brain stimulation as an experimental tool have improved our understanding of action control in the human brain and have important implications for treatment of patients with neurological disorders.
BRAF
V600E-induced distinct DNA damage response defines the therapeutic potential of p53 activation for TP53 wild-type colorectal cancer
Authors: Tokuyama Shinji , Kato Hisakazu , Takahashi Hidekazu , Ueda Kyoko , Arita Asami , Ueda Ryuta , Seto Hiroto , Sekido Yuki , Hata Tsuyoshi , Hamabe Atsushi , Ogino Takayuki , Miyoshi Norikatsu , Uemura Mamoru , Matsuoka Ken , Tsukamoto Osamu , Yamamoto Hirofumi , Doki Yuichiro , Eguchi Hidetoshi , Takashima Seiji
Published: June 2024

BRAF V600E, one of the most frequent mutations in the MAPK pathway, confers poor prognosis to colorectal cancers (CRCs), partly because of chemotherapeutic resistance. Oncogene-induced DNA damage responses (DDRs) that primarily activate p53 are important mechanistic barriers to the malignant transformation of cells; however, the mechanism underlying this impairment in cancer remains unknown. Here, we evaluated the responses of BRAFV600E-induced DDRs in two CRC cell lines, SW48 and LIM1215, both of which harbor wild-type TP53, KRAS, and BRAF. BRAFV600E transduction exhibited distinct phenotypes in these cells: SW48 cell proliferation markedly decreased, whereas that of LIM1215 increased. BRAFV600E expression induced the activation of oncogene-induced DDR signaling in SW48 cells, but not in LIM1215 cells, whereas chemotherapeutic agents similarly activated DDRs in both cell lines. Knockdown experiments revealed that these responses in SW48 cells were mediated by p53-p21 pathway activation. Comet assay (both alkaline and neutral) revealed that BRAFV600E increased single-strand breaks to the same extent in both cell lines; however, in the case of LIM1215 cells, it only facilitated double-strand breaks. Furthermore, the proliferation of LIM1215 cells, wherein no oncogene-induced DDRs occurred, was synergistically inhibited upon MDM2 inhibitor-mediated p53 activation combined with MEK inhibition. Taken together, these distinct DDR signaling responses highlight the novel characteristics of BRAFV600E-mutated CRC cells and define the therapeutic potential of p53 activation combined with MAPK inhibition against TP53 wild-type CRC harboring a BRAFV600E mutation.
Cumulative radiation dose from medical imaging in paediatric congenital heart disease patients with epicardial cardiac implantable electronic devices
Authors: Aboyewa Oluyemi B , Laternser Christina , Popescu Andrada , Murphy Nicole , Shah Dhaivat , Monge Michael C , Rigsby Cynthia K , Golestanirad Laleh , Webster Gregory , Kim Daniel
Published: June 2024

Aims

To determine whether paediatric congenital heart disease (CHD) patients with epicardial cardiac implantable electronic devices (CIEDs) receive high cumulative effective doses (CEDs) of ionizing radiation from medical imaging tests.

Methods and results

We compared 28 paediatric CHD patients with epicardial CIEDs (cases) against 40 patients with no CIED matched by age at operation, sex, surgical era, and CHD diagnosis (controls). We performed a retrospective review of radiation exposure from medical imaging exams between 2006 and 2022. Radiation dose from computed tomography (CT) and X-ray radiography was calculated using the National Cancer Institute Radiation Dosimetry Tool. We performed univariate analysis to compare the CED between the two groups. In the case subgroup, we convened experts’ review to adjudicate the prevalence of CT exams that should have been performed with magnetic resonance imaging (MRI) in the absence of a CIED. Children (median age 2.5 years at implant) with CIEDs received significantly higher median CED compared with matched controls (6.90 vs. 1.72 mSv, P = 0.0018). In cases, expert adjudication showed that 80% of the CT exams would have been performed with MRI in the absence of a CIED. This resulted, on average, a five-fold increase in the effective dose (ED) from post-lead implant CTs.

Conclusion

Paediatric CHD patients with CIED received four times higher CED than matched controls. Improved access to medical imaging tests without ionizing radiation, such as MRI, could potentially reduce the ED in CIED patients by up to five times.
Promoting interoperability between SNOMED CT and ICD-11: lessons learned from the pilot project mapping between SNOMED CT and the ICD-11 Foundation
Authors: Fung Kin Wah , Xu Julia , Brear Hazel , Lane Alana , Lau Maggie , Wong Austen , D'Havé Arabella
Published: June 2024

Objective

To explore the feasibility and challenges of mapping between SNOMED CT and the ICD-11 Foundation in both directions, SNOMED International and the World Health Organization conducted a pilot mapping project between September 2021 and August 2022.

Materials and Methods

Phase 1 mapped ICD-11 Foundation entities from the endocrine diseases chapter, excluding malignant neoplasms, to SNOMED CT. In phase 2, SNOMED CT concepts equivalent to those covered by the ICD-11 entities in phase 1 were mapped to the ICD-11 Foundation. The goal was to identify equivalence between an ICD-11 Foundation entity and a SNOMED CT concept. Postcoordination was used for mapping to ICD-11. Each map was done twice independently, the results were compared, and discrepancies were reconciled.

Results

In phase 1, 59% of 637 ICD-11 Foundation entities had an exact match in SNOMED CT. In phase 2, 32% of 1893 SNOMED CT concepts had an exact match in the ICD-11 Foundation, and postcoordination added 15% of exact match. Challenges encountered included non-synonymous synonyms, mismatch in granularity, composite conditions, and residual categories.

Conclusion

This pilot project shed light on the tremendous amount of effort required to create a map between the 2 coding systems and uncovered some common challenges. Future collaborative work between SNOMED International and WHO will likely benefit from its findings. It is recommended that the 2 organizations should clarify goals and use cases of mapping, provide adequate resources, set up a road map, and reconsider their original proposal of incorporating SNOMED CT into the ICD-11 Foundation ontology.
Resource requirements to accelerate clinical applications of next-generation sequencing and radiomics: workshop commentary and review
Authors: Harris Lyndsay , Shankar Lalitha K , Hildebrandt Claire , Rubinstein Wendy S , Langlais Kristofor , Rodriguez Henry , Berger Adam , Freymann John , Huang Erich P , Williams P Mickey , Zenklusen Jean Claude , Ochs Robert , Tezak Zivana , Sahiner Berkman
Published: June 2024

The National Institutes of Health–US Food and Drug Administration Joint Leadership Council Next-Generation Sequencing and Radiomics Working Group was formed by the National Institutes of Health–Food and Drug Administration Joint Leadership Council to promote the development and validation of innovative next-generation sequencing tests, radiomic tools, and associated data analysis and interpretation enhanced by artificial intelligence and machine learning technologies. A 2-day workshop was held on September 29-30, 2021, to convene members of the scientific community to discuss how to overcome the “ground truth” gap that has frequently been acknowledged as 1 of the limiting factors impeding high-quality research, development, validation, and regulatory science in these fields. This report provides a summary of the resource gaps identified by the working group and attendees, highlights existing resources and the ways they can potentially be employed to accelerate growth in these fields, and presents opportunities to support next-generation sequencing and radiomic tool development and validation using technologies such as artificial intelligence and machine learning.
Efficacy and safety of personalized optimal PD-(L)1 combinations in advanced NSCLC: a network meta-analysis
Authors: Chu Xianjing , Tian Wentao , Ning Jiaoyang , Zhou Rongrong
Published: June 2024

Introduction

Programmed death 1 (PD-1)/programmed death 1 ligand 1 (PD-L1)-directed immunotherapy has revolutionized the treatments for advanced non-small cell lung cancer (NSCLC), whereas the optimal therapeutic combinations remain uncertain.

Methods

Our study encompassed phase II/III randomized controlled trials (RCTs) that involved anti-PD-(L)1-based therapies for stage-IV NSCLC. The primary outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and incidences of adverse events. Subgroup analyses were conducted by treatment lines, PD-L1 expression levels, histological types, and metastatic sites.

Results

Our analysis incorporated 38 publications, covering 14 therapeutic combinations and involving 18 048 participants. PD-(L)1+chemotherapy (CT), PD-(L)1+ cytotoxic T lymphocyte-associated antigen-4 (CTLA4) +CT, and PD-(L)1+ T-cell immunoglobulin and ITIM domain were notably effective in prolonging OS. Overall, PD-(L)1+CT and PD-(L)1+CT+ vascular endothelial growth factor (VEGF) were significantly beneficial for PFS and ORR. As for the subsequent-line treatments, incorporating radiotherapy can enhance PFS and ORR (ranked fourth among enrolled treatments). For patients with PD-L1 <1%, PD-(L)1+CT+VEGF and PD-(L)1+CTLA4+CT were favorable approaches. Conversely, in patients with PD-L1 ≥50%, PD-(L)1+CT represented an effective treatment. Patients with nonsquamous cell carcinoma or liver metastases might benefit from the addition of VEGF. In cases of squamous cell carcinoma or brain metastases, the combination of PD-(L)1+CTLA4+CT yielded superior benefits.

Conclusions

This study underscores the enhanced efficacy of combination immunotherapies over monotherapy. It highlights the necessity for personalized treatment, considering individual factors. These insights are vital for clinical decision making in the management of advanced NSCLC.
A systematic review and meta-analysis of pediatric integrated primary care for the prevention and treatment of physical and behavioral health conditions
Authors: Hostutler Cody A , Shahidullah Jeffrey D , Mautone Jennifer A , Rybak Tiffany M , Okoroji Chimereodo , Bruni Teryn , Stephenson Kevin G , Utset Leah Vance , Freeman Kurt A , LaLonde Leah , Riley Andrew R
Published: June 2024

Objective

To evaluate the effects of behavioral health interventions delivered within pediatric integrated primary care models on clinical outcomes.

Methods

We searched Medline, EMBASE, CENTRAL, PsycINFO, and SCOPUS for studies published from January 1, 1998, to September 20, 2023. We included studies that evaluated onsite behavioral health integration in pediatric primary care using a comparator condition (usual, enhanced usual care, or waitlist). Outcome data on symptom change, impairment/quality of life, health indicator, and behavior change were extracted using Covidence software. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed Risk of bias analysis was conducted using the Cochrane Risk of Bias tool. We used multilevel meta-analysis to synthesize multiple outcomes nested within studies. Open Science Foundation pre-registration: #10.17605/OSF.IO/WV7XP.

Results

In total, 33 papers representing 27 studies involving 6,879 children and caregivers were included. Twenty-four studies were randomized controlled trials and three were quasi-experimental designs. Seventeen papers reported on treatment trials and 16 reported on prevention trials. We found a small overall effect size (SMD = 0.19, 95% confidence interval [0.11, 0.27]) supporting the superiority of integrated primary care to usual or enhanced usual care. Moderator analyses suggested similar effectiveness between co-located and integrated models and no statistically significant differences were found between treatment and prevention trials.

Conclusions

Results suggest that integrated primary care is superior to usual and enhanced usual care at improving behavior, quality of life, and symptoms. Integrated primary care research needs improved standards for reporting to promote better synthesis and understanding of the literature.
(426) CLINICAL FOLLOW-UP OF PATIENTS WITH MULTIPLE SCLEROSIS 10 YEARS AFTER PDE5IS TREATMENT FOR ERECTILE DYSFUNCTION: A REAL-LIFE COHORT STUDY
Authors: Thomas Charalampos , Kratiras Prof Zisis , Samarinas Michael , Diamantis Dr Georgios , Konstantinidis Charalampos
Published: June 2024

Objectives

Erectile Dysfunction (ED) is very common in patients suffering from Multiple Sclerosis (MS); the prevalence varies from 30% to almost 90%.Our aim was to study the adherence of MS patients to PDE5Is, in 10 years period.

Methods

119 MS patients suffering from ED that were treated with PDE5Is were evaluated in 2015. Concomitant cardiovascular diseases, hormonal and psychiatric disorders were excluded. Efficacy was evaluated with IIEF5 and SEP2&3 questions.

We re-evaluate our data now in order to assess the adherence to PDE5Is, almost 10 years after.

Results

10 years after we collected data from 94 patients out of the original 101 responders.

From the sildenafil group, 20 out of 36 are still on, 5 on daily tadalafil, 1 on intra-cavernosal injections (ICI), 1 died, 3 were lost from follow up, 1 underwent a 3-piece inflatable penile prosthesis insertion, 2 stopped due to lack of sexual partner and 3 stopped due to MS progression.

From the vardenafil group, 5/15 are still on, 2 on sildenafil, 2 on daily tadalafil, 1 on ICC, 3 without partner and 2 stopped due to progression.

From the avanafil group, 4/8 responders are still on, 1 ion sildenafil, 1 on daily tadalafil, 1 on ICC and 1 stopped to progression.

From the on demand tadalafil group, 7/18 are still on, 5 on daily tadalafil, 1 on sildenafil, 2 were lost from follow up, 1 on ICC, 1 without partner and 1 stopped due to progression.

From daily tadalafil group, 10/24 are still on, 1 is dead, 1 on ICC, 6 on sildenafil on, 1 underwent penile prosthesis, 2 without partner, 3 stopped due to progression.

Conclusions

After almost 10 years of follow up, the majority of our MS patients remained on PDE5 inhibitors, either the one prescribed initially or a different one. The medication dropout rate, in our cohort, is approximately 24%, while disease progression and lack of sexual partner were the major reasons for withdrawal.

Conflicts of Interest

None.
(349) LASER CIRCUMCISION: A NEW TECHNIQUE
Authors: Leonardi Prof Rosario , Iacona Dr Gabriele , Mondaini Prof Nicola , Saitta Dr Giuseppe
Published: June 2024

Objectives

Circumcision is a feasible and sometimes necessary surgical technique. In our practice we perform laser circumcision (LC) with good results.

Methods

We performed 52 laser circumcision (10/15 W, 1470 nm, 600 μ) between January 2021 and September 2023, considering functional outcomes (pain, bleeding, edema, fast recovery), operation time, good cosmesis and also comparing these results between different circumcision techniques: traditional surgery, glue, bipolar and lasers.

Results

There were no early postoperative morbidities, operation time was 15.8+-5.1 minutes, all patients were satisfied for the aesthetic results (p value <0.05).

Conclusions

LC seems to be more effective than other minimally invasive techniques in terms of safety, reproducibility of the technique, learning curve and reduced execution times, so we believe that laser use may become the ‘gold standard’ of circumcision.

Conflicts of Interest

No.
(267) PEDIATRIC URETHRAL STRICTURES - TREATMENT MODALITIES
Authors: Marjanovic Dr Marko , Kojovic Vladimir , Cvetinovic Dr Ana , Cico Dr Emre , Ilic Predrag
Published: June 2024

Objectives

Pediatric urethral strictures (US) are not a common problem and published series usually include small number of patients with short follow-up. Pediatric urethral reconstruction represents a great challenge due to anatomical characteristics of the pediatric urethra and small number of cases. The aim of this study is to present the surgical approaches for pediatric US.

Methods

From January 2007 until January 2023, 18 boys with US aged between 2 and 18 years were treated. Nine patients had US due to trauma, 7 patients underwent harmful iatrogenic procedures and 2 patients had a stricture of unknown cause. Patients with US due to complications of hypospadias repair were excluded. Stricture was presented on the anterior urethra in 14 and on the posterior urethra in 4 patients. Patients were treated with endoscopic intervention (2), augmentation using buccal mucosa graft (9) or urethrorrhaphy (7). Very short strictures of bulbar urethra were treated endoscopically (internal urethrotomy). More extensive bulbar strictures and obliterative posterior urethral disruption were treated by excision and primary anastomosis. The treatment method of the anterior US was urethral augmentation with buccal mucosa graft.

Results

The patients were followed for 12 to 160 months (mean 42 months). Quality of urinary stream, the presence of urinary tract infections or dysuria were recorded. If any disturbances were reported further exams were performed, uroflowmetry, urethrography and urethroscopy. Sixteen patients (89%) had good outcome, while two patients (11%) underwent redo procedure, one with endoscopic incision, and another with buccal mucosa graft augmentation. Complications as penile curvature, urethral fistula or diverticulum were not reported.

Conclusions

Pediatric US can be successfully treated by open surgery. Repeated dilatation and endoscopic treatment should not be preferred treatment method due to low success rate, possibility for additional injuries and non-compliance of the pediatric patients. For successful outcome of the US surgery individualized approach is required.

Conflicts of Interest

The authors declare no coflict of interest.
(365) THE EFFECTS OF A COLLEGE COURSE IN HUMAN SEXUALITY ON STUDENT’S KNOWLEDGE AND ATTITUDES
Authors: Fejza Prof Hajrullah , Icka Prof Ejona , Alidema Prof Fitim , Ukaj Prof Xhevat
Published: June 2024

Objectives

This article delves into the effects of a college course dedicated to human sexuality on students’ knowledge and attitudes.

Methods

The study was conducted at the UBT College in Pristina. Students (178), at the beginning of the first lecture and at the end of the course, answered 15 questions about their knowledge and attitudes about sexuality in the SKAT test (The Sex Knowledge and Attitude Test). After that, their answers were analyzed and tested with the SPSS before and after the test.

Results

In almost all questions, there is a big difference in their answers before and after the test. These are some of the questions with significant changes before and after the test. In the knowledge section most, relevant effects were shown when they were asked: Sexuality is usually a lifelong need -79.2 % vs 91%. Desire for sex in women can come after adequate stimulation from the partner - 59% vs 81%. Homosexuality is a disease and sexual deviation - 54.5 % vs. 31%. In the attitude section: It is better to start having sex after marriage – 59.6% vs. 39.9%. Contraception is the responsibility of both partners – 80% vs. 92.4%. Prostitution should be legalized – 28.7% vs. 34.8%.

Conclusions

The findings will contribute to the ongoing discourse surrounding the design and implementation of sexual education courses, aiding educators, policymakers, and institutions in refining their approaches to promoting informed and positive sexual attitudes among students.

Conflicts of Interest

The authors declare No conflict of interest.
FRET-guided modeling of nucleic acids
Authors: Steffen Fabio D , Cunha Richard A , Sigel Roland K O , Börner Richard
Published: June 2024

The functional diversity of RNAs is encoded in their innate conformational heterogeneity. The combination of single-molecule spectroscopy and computational modeling offers new attractive opportunities to map structural transitions within nucleic acid ensembles. Here, we describe a framework to harmonize single-molecule Förster resonance energy transfer (FRET) measurements with molecular dynamics simulations and de novo structure prediction. Using either all-atom or implicit fluorophore modeling, we recreate FRET experiments in silico, visualize the underlying structural dynamics and quantify the reaction coordinates. Using multiple accessible-contact volumes as a post hoc scoring method for fragment assembly in Rosetta, we demonstrate that FRET can be used to filter a de novo RNA structure prediction ensemble by refuting models that are not compatible with in vitro FRET measurement. We benchmark our FRET-assisted modeling approach on double-labeled DNA strands and validate it against an intrinsically dynamic manganese(II)-binding riboswitch. We show that a FRET coordinate describing the assembly of a four-way junction allows our pipeline to recapitulate the global fold of the riboswitch displayed by the crystal structure. We conclude that computational fluorescence spectroscopy facilitates the interpretability of dynamic structural ensembles and improves the mechanistic understanding of nucleic acid interactions.
Real-World Experience With Maribavir for Treatment of Cytomegalovirus Infection in High-Risk Solid Organ Transplant Recipients
Authors: Ni Bin , Wolfe Cameron R , Arif Sana , Carugati Manuela , Heldman Madeleine R , Messina Julia A , Miller Rachel A , Saullo Jennifer L , Baker Arthur W , Maziarz Eileen K
Published: June 2024

We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment failure due to treatment-emergent MBV resistance or early virological recurrence after MBV discontinuation occurred in 7 (47%) episodes. Sustained viral clearance was achieved in 6 (40%) episodes.
Therapeutic Myths in Solid Organ Transplantation Infectious Diseases
Authors: Goodlet Kellie J , McCreary Erin K , Nailor Michael D , Barnes Darina , Brokhof Marissa M , Bova Sarah , Clemens Evan , Kelly Beth , Lichvar Alicia , Pluckrose Dawn M , Summers Bryant B , Szempruch Kristen R , Tchen Stephanie
Published: June 2024

Infection management in solid organ transplantation poses unique challenges, with a diverse array of potential pathogens and associated antimicrobial therapies. With limited high-quality randomized clinical trials to direct optimal care, therapeutic “myths” may propagate and contribute to suboptimal or excessive antimicrobial use. We discuss 6 therapeutic myths with particular relevance to solid organ transplantation and provide recommendations for infectious diseases clinicians involved in the care of this high-risk population.
Measurement of temperature relaxation in the postshock plasma of the northwestern limb of SN 1006
Authors: Ichihashi Masahiro , Bamba Aya , Kato Yuichi , Katsuda Satoru , Suzuki Hiromasa , Kasuga Tomoaki , Odaka Hirokazu , Nakazawa Kazuhiro
Published: June 2024

Heating of charged particles via collisionless shocks, while ubiquitous in the universe, is an intriguing yet puzzling plasma phenomenon. One outstanding question is how electrons and ions approach an equilibrium after they were heated to different immediate-postshock temperatures. In order to fill the significant lack of observational information of the downstream temperature-relaxation process, we observe a thermal-dominant X-ray filament in the northwest of SN 1006 with Chandra. We divide this region into four layers with a thickness of $15^{\prime \prime }$ or $0.16\:$pc each, and fit each spectrum by a non-equilibrium ionization collisional plasma model. The electron temperature was found to increase toward downstream from 0.52–0.62 to 0.82–$0.95\:$keV on a length scale of $60^{\prime \prime }$ (or $0.64\:$pc). This electron temperature is lower than thermal relaxation processes via Coulomb scattering, requiring some other effects such as plasma mixture due to turbulence and/or projection effects, etc., which we hope will be resolved with future X-ray calorimeter missions such as XRISM and Athena.
Comparison of Operative and Nonoperative Management of Elderly Fragility Pelvic Ring Fractures
Authors: Swenson Riley A. , Paull Thomas Z. , Yates Rob A. , Foster Jeffrey A. , Griffin Jarod T. , Southall Wyatt G.S. , Aneja Arun , Nguyen Mai P.
Published: June 2024

OBJECTIVES:

To compare outcomes of nonoperative and percutaneous fixation of geriatric fragility lateral compression 1 (LC1) pelvic ring fractures.

METHODS:

Design:

Retrospective.

Setting:

Two level 1 trauma centers.

Patient Selection Criteria:

Included were patients who were 60 years or older with an isolated LC1 pelvic ring fracture managed nonoperatively or those who failed mobilization and were managed operatively with percutaneous sacral fixation. Patients with high-energy mechanisms of injury or polytrauma were excluded.

Outcome Measures and Comparisons:

The primary outcome was pain as measured by using the visual analog scale (VAS) after treatment. Secondary outcomes included length of stay, discharge disposition, mortality, readmission rates, and complications.

RESULTS:

In total, 231 patients were included with a mean age of 79.5 years (range 60–100). One hundred eighty-five (80.0%) patients were female. Sixty-two (26.8%) patients received percutaneous sacral fixation after failed mobilization, and 169 (73.2%) were managed nonoperatively. In the operative group, the median time to surgery was hospital day 4. Nonoperative patients were older (81.5 ± 10.0 years vs. 74.2 ± 9.4 years, P < 0.01) and had a shorter hospital length of stay (4.8 ± 6.2 days) than the operative group (10.6 ± 9.5 days, P < 0.01). Patients in the operative group had more pain (VAS 7.9 ± 3.0) than those in the nonoperative group (VAS 6.6 ± 3.0) (P = 0.01) on admission but had similar pain control postoperatively (VAS 4.4 ± 3.0) compared with the nonoperative group (VAS 4.5 ± 3.6) on the equivalent hospital day (P = 0.91). Thus, patients in the operative group experienced more improvement in pain (VAS 3.3 ± 2.7) compared with the nonoperative group (VAS 1.9 ± 3.9) after treatment (P = 0.02). Ninety-day mortality (P = 0.21) and readmission rates (P = 0.27) were similar for both groups. Two patients in the operative cohort sustained nerve injuries, whereas 1 patient in the nonoperative group had a nonunion and underwent surgery.

CONCLUSIONS:

Patients who undergo percutaneous surgical fixation for low-energy LC1 injuries have similar discharge disposition, mortality, complication rates, and readmission rates compared with patients treated nonoperatively. Percutaneous surgical fixation may provide significant pain relief for patients who failed conservative management.

LEVEL OF EVIDENCE:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Glass Tracing Alignment Method: A Novel, Low-Cost Coronal and Sagittal Alignment Transfer Method for Lower-Limb Prostheses
Authors: Habecker Matthew J.
Published: June 2024

Introduction

There are numerous ways to transfer the alignment of a lower-limb prosthesis that have been used and adapted over the last several decades. The proposed glass tracing alignment method (GTAM) allows for a convenient and rapid transfer of prosthetic alignment in the coronal and sagittal planes with minimal equipment requirements.

Objective

The aim of this article is to share a novel method for coronal and sagittal plane prosthetic alignment transfer, which may be done with minimal time, materials, and expense.

Materials and Methods

Prosthetic alignment may be transferred in part or in whole by tracing the prosthesis in both the coronal and sagittal planes. The prosthesis must first be stabilized on a surface that allows for the prosthetic foot to be traced and is adjacent to a wall surface that allows for tracing of the prosthesis proximal to the foot. The line of progression (LOP) of the prosthesis should be parallel to the edge of the table it is traced upon and in a vertical orientation when tracing the entire prosthesis in the sagittal plane. When tracing the coronal plane alignment, the foot should be oriented vertically and placed in the LOP. Sagittal and coronal tracings should include as much of the prosthesis as possible to insure the most accurate alignment transfer of components. The GTAM was developed to be a clinical complement to traditional alignment transfer methods, which may include use a vertical or horizontal prosthetic alignment transfer jig.

Results

Use of the described alignment tracing technique allows for the rapid alignment transfer of prosthetic componentry for a variety of applications.

Conclusions

The GTAM proposed is an easy way for a busy practitioner to certify that alignment transfers have been performed correctly or to preserve alignment when replacing elements of a prosthesis for clinical and/or research applications.

Clinical Relevance

It is expected that the GTAM will improve the clinical control, versatility, and scope of procedures related to referenced prosthetic and/or orthotic alignment to enhance the quality and consistency of patient outcomes.
Posterior tongue tie: that is a thing?
Authors: Black Kaelan
Published: June 2024

Purpose of review

The purpose of this review is to examine the current research of the posterior tongue tie and how it relates to breast feeding, solid feeding, and speech.

Recent findings

Recent findings show that the posterior tongue tie may play a role in effective breast feeding.

Ankyloglossia is the term used for the restriction of the movement of the tongue that impairs certain functions such as breastfeeding or bottle feeding, feeding with solids, and speech. Cadaver studies have shown that there can be a restriction of the tongue and oral tissues in some people relative to others. In some breast-feeding studies, releasing the posterior tie has been shown to improve certain aspects of tongue movement. There is little evidence for or against posterior tongue ties contributing to other problems such as speech and solid feeding. This article goes into depth about the current studies on posterior ankyloglossia.
Longitudinal viral load outcomes of adults with HIV after detectable viremia on tenofovir, lamivudine, and dolutegravir
Authors: Sodeke Olutomi , Milligan Kyle , Ezeuko Ijeoma , Oladipo Ademola , Emeh Anuri , Bashorun Adebobola , Orisawayi Oluwaniyi , Danjuma Sanda , Onotu Dennis , Boyd Adetinuke Mary , Abutu Andrew , Chun Helen , Vallabhaneni Snigdha
Published: June 2024

Background:

To inform optimal management of HIV viremia on tenofovir, lamivudine, and dolutegravir (TLD), we examined viral load (VL) outcomes of a large cohort of adult PWH on TLD in Nigeria.

Methods:

We conducted a retrospective study of adult PWH who had ≥1 VL after initiating TLD during January 2017–February 2023. VLs were categorized as undetectable (≤50 copies/ml), low low-level viremia (LLV, 51–199 copies/ml), high LLV (200–999 copies/ml), virologic nonsuppression (VLNS, ≥1000 copies/ml), and virologic failure (VF, ≥2 consecutive VLNS results). Among patients with ≥2 VLs on TLD, we described how viremia changed over time and examined virologic outcomes after VF. We identified predictors of subsequent VLNS using mixed-effects logistic regression and conducted planned contrasts between levels of VL result and regimen types.

Results:

Analysis of 82,984 VL pairs from 47,531 patients demonstrated viral resuppression to ≤50 copies/ml at follow-up VL in 66.7% of those with initial low LLV, 59.1% of those with initial high LLV, and 48.9% of those with initial VLNS. Of 662 patients with a follow-up VL after VF, 94.6% stayed on TLD; of which 57.8% (359/621) were undetectable at next VL without regimen change. Previous low LLV [adjusted odds ratio (aOR) 1.74, 1.56–1.93], high LLV (aOR 2.35, 2.08–2.65), and VLNS (aOR 6.45, 5.81–7.16) were associated with increasingly higher odds of subsequent VLNS, whereas a previously undetectable VL (aOR 1.08, 0.99–1.71) on TLD was not.

Conclusions:

Despite increased odds of subsequent VLNS, most PWH with detectable viremia on TLD, including those with VF, will resuppress to an undetectable VL without a regimen change.
Immune Checkpoint Inhibitors–Associated Generalized Lipodystrophy: Reconstructive Challenges of an Emerging and Distinct Form of Lipodystrophy
Authors: Kreutz-Rodrigues Lucas , Cherukuri Sai , Rames Jess D. , Chen Austin , Meira Pazelli Alexandre , Mardini Samir , Gibreel Waleed
Published: June 2024

Total and permanent loss of facial and nonfacial fat is a rare side effect of immune checkpoint inhibitors (ICIs). Consequently, effective treatment modalities for patients remain undefined. Here, we discuss the surgical treatment of a patient with both ICI-related acquired generalized lipodystrophy (AGL). We additionally performed a comprehensive literature review (Cochrane, Embase, and MEDLINE) to summarize what is known about ICI-related lipodystrophy and available treatments for this rare complication. A 66-year-old female diagnosed with metastatic lung adenocarcinoma started ICI (pembrolizumab) treatment. She developed generalized lipodystrophy 13 months after her first cycle. Her primary concern was the loss of facial fat volume, which significantly aged her appearance. The patient underwent a 2-staged restoration of her facial fat compartments using dermal grafts from the lower abdomen and medial thighs. The patient recovered uneventfully and was satisfied with the aesthetic improvement at 18 months of follow-up. The authors identified 8 case reports with patients with ICI-AGL. The mean age was 53.63 years, and the mean BMI was 36.72 kg/m2. The average onset of symptoms was 7.44 months after ICI initiation. None of the studies described any sort of surgical or nonsurgical options to restore the volume of the facial fat compartments. The management of combined facial and nonfacial lipodystrophy remains challenging due to the lack of suitable autologous fat donor sites. In this report, the authors demonstrate that staged volume restoration can be achieved using autologous dermal grafts from the thigh, making it a viable reconstructive option in this subset of patients.
Management of Limited Mouth Opening After Open Reduction and Fixation of Mandibular Coronoid Fractures
Authors: Zhang Difei , Lv Kun
Published: June 2024

Mandibular coronoid process fractures are relatively rare and generally treated conservatively. This paper reports a case of limited mouth opening and pain after open reduction and fixation of the mandibular coronoid fracture. After the loose titanium screws, plates, and absorbed coronoid fracture fragments were removed, the patient’s mouth opening was restored immediately. The authors believe that open reduction and fixation for coronoid process fractures can cause postoperative limited mouth opening and pain. Conservative treatment of coronoid process fractures is more beneficial for patients.
An Enhanced Role of Innate Immunity in the Immune Response After Kidney Transplant in People Living With HIV: A Transcriptomic Analysis
Authors: Zarinsefat Arya , Dobi Dejan , Kelly Yvonne M. , Szabo Gyula , Henrich Timothy , Laszik Zoltan G. , Stock Peter G.
Published: June 2024

Background.

Although kidney transplantation (KT) has become the standard of care for people living with HIV (PLWH) suffering from renal failure, early experiences revealed unanticipated higher rejection rates than those observed in HIV− recipients. The cause of increased acute rejection (AR) in PLWH was assessed by performing a transcriptomic analysis of biopsy specimens, comparing HIV+ to HIV− recipients.

Methods.

An analysis of 68 (34 HIV+, 34 HIV−) formalin-fixed paraffin-embedded (FFPE) renal biopsies matched for degree of inflammation was performed from KT recipients with acute T cell-mediated rejection (aTCMR), borderline for aTCMR (BL), and normal findings. Gene expression was measured using the NanoString platform on a custom gene panel to assess differential gene expression (DE) and pathway analysis (PA).

Results.

DE analysis revealed multiple genes with significantly increased expression in the HIV+ cohort in aTCMR and BL relative to the HIV− cohort. PA of these genes showed enrichment of various inflammatory pathways, particularly innate immune pathways associated with Toll-like receptors.

Conclusions.

Upregulation of the innate immune pathways in the biopsies of PLWH with aTCMR and BL is suggestive of a unique immune response that may stem from immune dysregulation related to HIV infection. These findings suggest that these unique HIV-driven pathways may in part be contributory to the increased incidence of allograft rejection after renal transplantation in PLWH.
Antidepressants in the acute treatment of post-traumatic stress disorder in adults: a systematic review and meta-analysis
Authors: Guidetti Clotilde , Feeney Anna , Hock Rebecca S. , Iovieno Nadia , Hernández Ortiz Jesús M. , Fava Maurizio , Papakostas George I.
Published: June 2024

Currently, there are few pharmacotherapy options for clinicians treating post-traumatic stress disorder (PTSD), and antidepressants are usually the medication of choice. This meta-analysis aimed to review the efficacy of antidepressants in the acute treatment of PTSD in adults while investigating the contribution of study design and placebo response to the findings of these studies. Randomized, double-blind, placebo-controlled clinical trials that compared antidepressants with placebo for acute treatment of PTSD were selected. Standardized mean difference (SMD) in change in Clinician-Administered PTSD Scale scores were pooled after examining for heterogeneity. A random-effects meta-analysis was performed. Twenty-nine antidepressant-placebo comparisons, involving 4575 subjects, were analyzed. The SMD among all studies was 0.25, a small to medium effect size, lower than that in studies of antidepressants in adult major depressive disorder. The SMDs for low and high mean placebo responses, were 0.27 and 0.22, respectively. The overall SMD for paroxetine studies was in the moderate range (0.43) and that for sertraline studies was in the small range (0.12). Our findings suggest that antidepressants have modest efficacy in alleviating PTSD symptoms. Patient-level meta-analyses are required to further explore the potential clinical relevance of sertraline for PTSD.
Fatal Clostridium septicum gas gangrene complicating ECMO: case report and review of literature
Authors: Turban Adrien , Joussellin Vincent , Piau Caroline , Cattoir Vincent , Launey Yoann , Eustache Gabriel
Published: June 2024

Clostridium septicum gas gangrene is a severe and deadly infection caused by an anaerobic, spore-forming, Gram-positive bacillus. As previously described, two entities are observed: traumatic and spontaneous (or non-traumatic) forms. In this report, we aim to describe the case of a fulminant and ultimately fatal C. septicum myonecrosis occurring in a patient who was first admitted for refractory cardiac arrest and placed on veino-arterial extracorporeal membrane oxygenation (ECMO). Building upon prior studies that have documented cases of spontaneous gas gangrene caused by C. septicum, we provide an updated compilation, focusing on microbiological characteristics of C. septicum, along with the diagnostic and therapeutic challenges associated with spontaneous gas gangrene. Additionally, the specific clinical situation of our case illustrates the seriousness of this infectious complication that combined both spontaneous and traumatic gas gangrene risk factors. We thus, discuss the antibiotic coverage prior to the initiation of ECMO procedure.