bluuebunny/crossref_metadata_2025 huggingface dataset:
Opalski syndrome: a rare variant of Wallenberg syndrome: a case report and literature review
Authors: Mansour Marah , Alwaw Ricarda , Almaalouli Bsher , Qasem Yasmine , Hassan Khalil , Charaf Obada , Chama Mohd Beshr , Mansour Nawar Akramah , allabwani Abd alqader , Hammad Yousha
Published: June 2024

Background:

Opalski syndrome is a rare variant of Wallenberg syndrome (lateral medullary syndrome) that demonstrates concomitant ipsilateral hemiplegia due to infarctions within the lateral medulla and the cervical spinal cord, which also extend to the post-pyramidal decussation to affect the corticospinal tract.

Case presentation:

A 56-year-old man initially presented with a unilateral headache with right cervical pain. Consequently, he developed symptoms that indicate Wallenberg syndrome: vertigo, dysphonia, dysarthria, right limb ataxia with a tendency to fall, and ptosis, in addition to ipsilateral hemiparesis. The diffusion-weighted imaging MRI (DWI MRI) performed initially demonstrated an acute infarct in the dorsolateral medulla. Accordingly, an axial T2-weighted MRI showed a hyperintense focal region in the same area, even as magnetic resonance angiography (MRA) revealed complete stenosis of the corresponding vertebral artery.

Discussion:

Opalski syndrome can result from different etiologies such as vascular occlusion or dissection. Although symptoms may vary, patients commonly present with sudden weakness, vertigo, and gait instability. Diagnosis often relies on MRI or DW-MRI. Treatment is tailored depending on individual factors and may involve medications and monitoring. Complications like respiratory failure can occur but are not directly linked to Opalski syndrome. Proper management includes addressing ischemic risk factors and ensuring appropriate nutrition.

Conclusion:

This case highlights the importance of including Opalski syndrome early in the differential diagnosis of patients with clinically suspected ipsilateral lateral medullary infarction and hyperacute ipsilateral hemiparesis.
Community-Based Palliative Care
Authors: Fasolino Tracy , Hollinger Wayne , Boota Ahmad , Steeves Cindy M.
Published: June 2024

Community-based palliative care (CBPC) models address the growing needs of patients and caregivers with chronic and serious illnesses. From pediatrics to geriatrics, individuals prefer to receive care within their local community and at home. Delivering care at the community level and within the home improves health outcomes, reduces disparities, and supports local economic activity. Various models of CBPC have developed through partnerships with existing services, such as home health agencies, but ongoing challenges and barriers exist for further expansion of specialty palliative care. Advanced practice registered nurses increasingly manage chronic and serious illnesses and are essential for all health care teams, particularly for CBPC. As trusted providers within the community, advanced practice registered nurses create lasting relationships that allow for meaningful exchanges with patients and caregivers. This article reviewed the concept and features of CBPC offered within the United States and describes an advanced practice registered nurse–led embedded palliative care program for advanced lung disease.
A comparison of textured vs smooth surfaced implants in sub fascial breast augmentation.
Authors: Brown Tim
Published: June 2024

Background:

Subfascial placement of breast implants has the advantages of subglandular and submuscular placement without the adverse outcomes. This study examined the differences in outcomes between textured and smooth implants.

Methods:

A total of 385 patients underwent subfascial breast augmentation in two cohorts. The initial series (n=209) employed textured implants and the second (n=176) employed smooth implants. In all other respects, patient management was identical. Adverse outcomes, changes in breast morphometry, and patient satisfaction were compared between the two groups.

Results:

The follow-up period ranged from to 74-272 weeks for smooth implants (mean 164 weeks, STD 50.6) and 78-279 weeks for textured implants (mean= 186 weeks, STD=54). The incidence of capsular contracture was the same for smooth and textured implants (4.7% and 6.2%, P=.64). Changes in breast shape at the lower pole, patient satisfaction, and the incidence of other adverse outcomes were the same in both groups.

Conclusions:

Subfascial placement of smooth and textured breast implants yielded similar outcomes.
Peer-Delivered HIV Self-Testing, Sexually Transmitted Infection Self-Sampling, and Pre-exposure Prophylaxis for Transgender Women in Uganda: A Randomized Trial
Authors: Mujugira Andrew , Karungi Beyonce , Nakyanzi Agnes , Bagaya Monica , Nsubuga Rogers , Sebuliba Timothy , Nampewo Olivia , Naddunga Faith , Birungi Juliet E. , Sapiri Oliver , Nyanzi Kikulwe R. , Bambia Felix , Muwonge Timothy , Gandhi Monica , Haberer Jessica E.
Published: June 2024

Background:

Peer-delivered HIV self-testing (HIVST) and sexually transmitted infection self-sampling (STISS) may promote adherence to oral pre-exposure prophylaxis (PrEP), but no studies have analyzed this approach among transgender women (TGW) in sub-Saharan Africa.

Setting:

The Peer study was a cluster randomized trial in Uganda (October 2020–July 2022; NCT04328025).

Methods:

Ten TGW peer groups, each with 1 TGW peer and 8 TGW, were randomized 1:1 to receive quarterly in-clinic HIV testing with PrEP refills as standard-of-care (SOC) or SOC plus monthly peer delivery of oral-fluid HIVST, STISS, and PrEP refills (intervention). Participants were followed for 12 months. The primary outcome was PrEP adherence.

Results:

We screened 85 TGW and enrolled 82 (41 per arm). The median age was 22 years (interquartile range [IQR] 20–24). Twelve-month retention was 88% (72/82). At the 3, 6, 9, and 12-month clinic visits, 10%, 5%, 5%, and 0% of TGW in the intervention arm had TFV-DP levels ≥700 fmol/punch, versus 7%, 15%, 7%, and 2% in the SOC arm, respectively (P = 0.18). At all visits, any detectable TFV-DP levels were significantly higher in SOC than the peer delivery group (P < 0.04). PrEP adherence was associated with sex work (incidence rate ratio 6.93; 95% CI: 2.33 to 20.60) and >10 years of schooling (incidence rate ratio 2.35; 95% CI: 1.14 to 4.84). There was a strong correlation between tenofovir detection in dried blood spots and urine (P < 0.001). No HIV seroconversions occurred.

Conclusions:

Peer-delivered HIVST and STISS did not increase low levels of oral PrEP adherence among TGW in Uganda. Long-acting PrEP formulations should be considered for this population.
Mental Health Trends in Patients With Symptomatic Macromastia After Reduction Mammoplasty
Authors: Park Rachel H. , Odega Ugochukwu K. , Kilmer Lee H. , Hollenbeck Scott T. , DeGeorge Brent R.
Published: June 2024

Background

Symptomatic macromastia can significantly affect both physical and mental health. Although previous studies suggested that breast reduction (BR) improves quality of life and mental health conditions, they were limited to smaller sample sizes and largely based on survey feedback. This study aims to further assess the impact of BR on mental health outcomes, specifically looking at prescribing patterns for common antidepressants.

Methods

A national insurance–based database was utilized for data collection. Patients with a diagnosis of macromastia (ICD-10 N62) between the years 2010 and 2021 that either underwent bilateral BR (CPT 19318) or did not undergo BR were included in the study. Demographics and medical comorbidities were compared. Among those who underwent BR, preoperative and postoperative rates of mental health diagnoses and antidepressant use were compared. Logistic regression analysis was performed to determine variables associated with surgery.

Results

Patients with a history of macromastia with a history of BR were compared with those with a history of macromastia without BR. A significantly higher percentage of patients in the BR group reported a history of depression (48.5%), obesity (55.7%), and selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) use (55.3%) when compared with that of the no-reduction group (46.3%, 50.8%, and 52.6%). Patients with history of depression and obesity were more likely to undergo BR (odds ratio of 1.11 and 1.31). Patients who underwent BR had significantly reduced rates of mental health outcomes including depression (38.6% to 27.4%), anxiety (4.3% to 3.1%), and SSRI or SNRI prescriptions (46.3% to 29.5%) postoperatively.

Conclusions

Patients who underwent BR for symptomatic macromastia showed significantly reduced rates of depression, anxiety, and most importantly, rates of SSRI/SNRI prescriptions postoperatively when compared to those who did not undergo BR for symptomatic macromastia.
Anatomy of the Buccal Space: Surgical and Radiological Perspectives
Authors: Kim Chung Yoh , Takeshita Yohei , Kugimoto Takuma , Harada Hiroyuki , Park Jin Seo , Tubbs R. Shane , Iwanaga Joe
Published: June 2024

Among the anatomical spaces in the head and neck area, the buccal space has often been studied in dental/oral surgery and cosmetic surgery because it contains the facial vessels, mandibular and facial nerves, and adipose tissue called the buccal fat pad. In addition, as the space can communicate with other spaces, it can be significant in infections. Although the anatomy of the buccal space has been reported in several studies, there have been discrepancies concerning its boundaries, and its communications have often been overlooked. The aim of this review is to examine the anatomy of buccal space including its boundaries, contents, continuity with adjacent spaces, and clinical significance. A literature review was performed on Google Scholar and PubMed. The literature has depicted the anterior, medial, and lateral boundaries more or less consistently, but descriptions of the posterior, superior, and inferior borders are controversial. The buccal space includes the facial arteries, veins, facial nerves, parotid duct, and lymph nodes, which can be described differently depending on definitions and the extent of the space. As it communicates with other anatomical spaces including the masticatory space, it can be a reservoir and a channel for infections and tumors. Buccal fat pads have various clinical applications, from a candidate for flap reconstruction to a target for removal for cosmetic purposes. This review will help understand the anatomy of the buccal space including its boundaries, residing structures, and communication with other spaces from surgical and radiological perspectives.
Entrustable Professional Activities in Postgraduate General Surgery Training
Authors: Nel Daniel , Jonas Eduard , Burch Vanessa , Cairncross Lydia , Nel Amy , Alseidi Adnan , George Brian , ten Cate Olle
Published: June 2024

Objective:

To provide an overview of the current use of Entrustable Professional Activities (EPAs) in postgraduate general surgery training internationally.

Background:

Entrustable Professional Activities (EPAs) were introduced to connect clinical competencies and the professional activities to be entrusted to trainees on graduation. The popularity of EPAs as a framework for assessment is growing globally, including in general surgery. Anecdotally, there appears to be substantial variation in how they are implemented, yet a formal comparison of their use in postgraduate general surgery training is lacking.

Methods:

A scoping review was performed, based on the original five-stage approach described by Arksey and O’Malley with the addition of protocol-specific items from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols extension for scoping reviews (PRISMA-ScR).

Results:

Twenty-nine published and grey literature sources were included in the review. Entrustable Professional Activity use in postgraduate general surgery training was identified in 11 unique contexts, including from North America, South America, Europe, Asia, Africa, and Australia. There were substantial differences in the scope and number of EPAs, tools used for EPA assessment, and how EPAs were sequenced through training. Despite wide variation, eight distinct EPAs were common to the majority (>80%) of countries. Several articles described findings of EPA use in postgraduate general surgery training, allowing identification of multiple barriers and facilitators to integration.

Conclusions:

This review provides guidance for certification and regulatory bodies, program directors, and institutions with ambitions to implement EPAs for assessment and curricular design. In settings where EPAs are already used, the data may facilitate refinement of programs and strategies.
A microbiome-directed therapeutic food for children recovering from severe acute malnutrition
Authors: Hartman Steven J. , Hibberd Matthew C. , Mostafa Ishita , Nahar Naila N. , Islam Md. Munirul , Uz Zaman Mahabub , Huq Sayeeda , Mahfuz Mustafa , Islam Md. Tazul , Mukherji Kallol , Moghaddam Vaha Akbary , Chen Robert Y. , Province Michael A. , Webber Daniel M. , Henrissat Suzanne , Henrissat Bernard , Terrapon Nicolas , Rodionov Dmitry A , Osterman Andrei L. , Barratt Michael J. , Ahmed Tahmeed , Gordon Jeffrey I.
Published: June 2024

Severe acute malnutrition (SAM), defined anthropometrically as a weight-for-length z-score more than 3 standard deviations below the mean (WLZ<-3), affects 19 million children under 5-years-old worldwide. Complete anthropometric recovery after standard inventions is rare with children often left with moderate acute malnutrition (MAM; WLZ -2 to -3). Here we conduct a randomized controlled trial (RCT), involving 12-18-month-old Bangladeshi children from urban and rural sites, who after hospital-based treatment for SAM received a 3-month intervention with a microbiota-directed complementary food (MDCF-2) or a ready-to-use supplementary food (RUSF) as they transitioned to MAM. The rate of WLZ improvement was significantly greater with MDCF-2 than the more calorically-dense RUSF, as we observed in a previous RCT of Bangladeshi children with MAM without antecedent SAM. A correlated meta-analysis of aptamer-based measurements of 4,520 plasma proteins in this and the prior RCT revealed 215 proteins positively-associated with WLZ (prominently those involved in musculoskeletal and CNS development) and 44 negatively-associated proteins (related to immune activation), with a significant enrichment in levels of the positively WLZ-associated proteins in the MDCF-2 arm. Characterizing changes in 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome, its transition as each child achieves a state of MAM, and how specific strains of Prevotella copri function at the intersection between MDCF-2 glycan metabolism and the rescue of growth faltering. These results provide a rationale for further testing the generalizability of the efficacy of MDCF and identify biomarkers for defining treatment responses.
Performance evaluation of TaqMan™Arbovirus Triplex Kit (ZIKV/DENV/CHIKV) for detection and differentiation of Dengue and Chikungunya viral RNA in serum samples of symptomatic patients
Authors: Panmei Kakhangchung , Hakeem Syed Abdul , Okafor Obiageli , Mammen Shoba , Abraham Asha Mary
Published: June 2024

Introduction

Global outbreaks of mosquito-transmitted arbovirus infections, such as dengue (DENV) and chikungunya (CHIKV), are increasing. Differentiating these infections is challenging due to non-specific symptoms and serology limitations. PCR-based approaches offer higher sensitivity and specificity. This study evaluated the performance of TaqMan™ Arbovirus Triplex Kit (ZIKV/DENV/CHIKV) (TaqMan™ Kit) to detect DENV and CHIKV in clinical samples from patients in south India.

Methods

In total, 280 serum samples with 90 DENV-positive, 90 CHIKV-positive, and 100 negative samples were tested with TaqMan™ Kit and CDC Trioplex Real-Time RT-PCR assay. No Zika virus was detected. The sensitivity and specificity of viral RNA detection were determined, and discordant results were resolved using comparator PCRs, dengue NS1 antigen detection, virus-specific antibody results, or previously de-identified in-house PCR results.

Results

The TaqMan™ Kit showed 100% agreement with the comparator for DENV detection in 92 positive samples. Among 188 samples negative for DENV by the comparator, 30 showed positive results with the TaqMan™ kit, and 23 of those were confirmed as true positives. The resulting sensitivity and specificity for DENV detection were 100% and 95.1%, respectively. For CHIKV, 77 positive and 195 negative results were concordant. Eight samples showed discordant results, but upon resolution testing, sensitivity and specificity for CHIKV were 93.9% and 100.0%, respectively.

Conclusion

The TaqMan™ Arbovirus Triplex Kit demonstrated high sensitivity and specificity (>93%) for detecting circulating DENV and CHIKV strains. Multiplex PCR testing can improve case detection, surveillance, and public health responses while optimizing laboratory resources for outbreak control.
Factors involved in vulvar pain during sexual activity and persistence in sexual activity amidst pain
Authors: Oesterling Carlotta , Harder Amelie , Borg Charmaine , de Jong Peter
Published: June 2024

Evidence suggests that women often endure pain during sexual activity, continue engaging in such activity despite experiencing pain, and tend to avoid communicating these painful experiences to their partners. The present study aims to shed light on psychosocial factors that may contribute to vulvar pain and the engagement in sexual activity despite pain, with a specific focus on the relevance of sexual self-esteem, the definition of sex (limited to penile-vaginal intercourse or inclusive of other intimate behaviours), sexual agency, and sexual motivation. A sample of N = 277 female students of a Dutch University was included. Participants were between 18 and 33 years old. The primary outcome measures were female sexual distress, sexual function, and vulvar pain. Engagement in sexual activity despite pain, pain communication, sexual agency, and relationship satisfaction were included as mediators. The majority of participants (80%) reported to experience pain at least sometimes, and 15% reported to experience pain more than half of the time. Engaging in penile-vaginal intercourse despite experiencing pain was common, with 42% of participants indicating to do so always or most of the time and 65% at least sometimes when experiencing pain. Of the affected women, 41% did not communicate pain to their partners. Low sexual self-esteem, a restrictive definition of sex, limited sexual agency, and low autonomous sexual motivation were all significantly related to at least one of the primary outcome variables. These associations were partly mediated by engagement in PVI despite pain, (no) pain communication, and (low) relationship satisfaction.
Defining the Regulatory Logic of Breast Cancer Using Single-Cell Epigenetic and Transcriptome Profiling
Authors: Regner Matthew J. , Garcia-Recio Susana , Thennavan Aatish , Wisniewska Kamila , Mendez-Giraldez Raul , Felsheim Brooke , Spanheimer Philip M. , Parker Joel S. , Perou Charles M. , Franco Hector L.
Published: June 2024

Annotation of thecis-regulatory elements that drive transcriptional dysregulation in cancer cells is critical to improving our understanding of tumor biology. Herein, we present a compendium of matched chromatin accessibility (scATAC-seq) and transcriptome (scRNA-seq) profiles at single-cell resolution from human breast tumors and healthy mammary tissues processed immediately following surgical resection. We identify the most likely cell-of-origin for luminal breast tumors and basal breast tumors and then introduce a novel methodology that implements linear mixed-effects models to systematically quantify associations between regions of chromatin accessibility (i.e. regulatory elements) and gene expression in malignant cells versus normal mammary epithelial cells. These data unveil regulatory elements with that switch from silencers of gene expression in normal cells to enhancers of gene expression in cancer cells, leading to the upregulation of clinically relevant oncogenes. To translate the utility of this dataset into tractable models, we generated matched scATAC-seq and scRNA-seq profiles for breast cancer cell lines, revealing, for each subtype, a conserved oncogenic gene expression program betweenin vitroandin vivocells. Together, this work highlights the importance of non-coding regulatory mechanisms that underlie oncogenic processes and the ability of single-cell multi-omics to define the regulatory logic of BC cells at single-cell resolution.
DecipheringArabidopsis thalianaAcclimation to Sublethal Combined Abiotic Stresses
Authors: Jiang Zhang , Verhoeven Ava , Li Yihong , Geertsma Romy , Sasidharan Rashmi , van Zanten Martijn
Published: June 2024

Plants are frequently exposed to environmental challenges. Responses to sub-lethal abiotic stress combinations are complex and often distinct from responses to individual stresses and remain poorly understood. Investigating traits and molecular factors mediating acclimation to stress combinations is essential for the development of climate change-resilient field crops. Here, we studied the morphological, physiological, and molecular responses ofArabidopsis thalianato i) co-occurring high temperature and drought and ii) flooding sequentially followed by drought, both of which have increased in frequency due to climate change. A set of 15 physiological and morphological traits were assessed during single and combined stresses. By combining these comprehensive trait analyses with transcriptome characterization, we established the generally additive effects of simultaneous or sequential stresses on plant morphology and physiology compared to the corresponding individual stresses. Although drought had a mild effect in both stress combinations, a unique transcriptome signature emerged upon combination with high temperature simultaneously or flooding sequentially. Molecular processes identified as important for multi-stress resilience included plastid-nucleus communication, ABA signaling and photo-acclimation. Based on the RNA-seq data, a set of 39 genes was identified as potential multi-stress response regulators. Mutants were tested to validate their contribution to plant survival and phenotypic acclimation under combined stress. We confirmed the involvement of several genes in regulating phenotypic acclimation traits. Among the novel identified factors are EARLY FLOWERING 6 (ELF6) and ARABIDOPSIS TÓXICOS EN LEVADURA (ATL80), with significant effects on plant growth, leaf development and plant survival (wilting) during high-temperature drought and post-submergence drought respectively.
ESPRESSO: Spatiotemporal omics based on organelle phenotyping
Authors: Scipioni Lorenzo , Tedeschi Giulia , Navarro Mariana , Jia Yunlong , Atwood Scott , Prescher Jennifer A. , Digman Michelle
Published: June 2024

Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, have been instrumental to improving our understanding of complex biological systems. Despite fast-pace advancements, a crucial dimension is still left to explore: time. To capture this key parameter, we introduce ESPRESSO (Environmental Sensor Phenotyping RElayed by Subcellular Structures and Organelles), a pioneering technique that provides high-dimensional phenotyping resolved in space and time. Through a novel paradigm, ESPRESSO combines fluorescent labeling, advanced microscopy and bioimage and data analysis to extract morphological and functional information of the organelle network unveiling phenotypic changes over time at the single-cell level. In this work, we present ESPRESSO’s methodology and its application across numerous cellular systems, showcasing its ability to discern cell types, stress response, differentiation and immune cells polarization. We then correlate ESPRESSO phenotypic changes with gene expression and demonstrate its applicability to 3D cultures, offering a path to revolutionizing biological exploration, providing invaluable insights into cellular states in both space and time.
Enhancing Mass Vaccination Programs with Queueing Theory and Spatial Optimization
Authors: Xie Sherrie , Rieders Maria , Changolkar Srisa , Bhattacharya Bhaswar B. , Diaz Elvis W. , Levy Michael Z. , Castillo-Neyra Ricardo
Published: June 2024

Background

Mass vaccination is a cornerstone of public health emergency preparedness and response. However, injudicious placement of vaccination sites can lead to the formation of long waiting lines orqueues, which discourages individuals from waiting to be vaccinated and may thus jeopardize the achievement of public health targets. Queueing theory offers a framework for modeling queue formation at vaccination sites and its effect on vaccine uptake.

Methods

We developed an algorithm that integrates queueing theory within a spatial optimization framework to optimize the placement of mass vaccination sites. The algorithm was built and tested using data from a mass canine rabies vaccination campaign in Arequipa, Peru. We compared expected vaccination coverage and losses from queueing (i.e., attrition) for sites optimized with our queue-conscious algorithm to those obtained from a queue-naive version of the same algorithm.

Results

Sites placed by the queue-conscious algorithm resulted in 9-19% less attrition and 1-2% higher vaccination coverage compared to sites placed by the queue-naïve algorithm. Compared to the queue-naïve algorithm, the queue-conscious algorithm favored placing more sites in densely populated areas to offset high arrival volumes, thereby reducing losses due to excessive queueing. These results were not sensitive to misspecification of queueing parameters or relaxation of the constant arrival rate assumption.

Conclusion

One should consider losses from queueing to optimally place mass vaccination sites, even when empirically derived queueing parameters are not available. Due to the negative impacts of excessive wait times on participant satisfaction, reducing queueing attrition is also expected to yield downstream benefits and improve vaccination coverage in subsequent mass vaccination campaigns.
Style deflection is determined by the handedness of phyllotaxis and auxin-induced differential cell elongation in a species with mirror-image flowers
Authors: Robertson Caroline , Xue Haoran , Saltini Marco , Fairnie Alice L. M. , Lang Dirk , Kerstens Merijn H. L. , Willemsen Viola , Ingle Robert A. , Barrett Spencer C. H. , Deinum Eva E. , Illing Nicola , Lenhard Michael
Published: June 2024

Many animals and plants show left-right (LR) asymmetry. In some animal systems, handedness has a simple genetic basis, which has allowed identifying how handedness is determined at the molecular level, even if its functional relevance often remains unclear. Mirror-image flowers represent an example of LR asymmetry of clear functional significance, with the reciprocal placement of male and female organs in left- versus right-handed flowers promoting cross-pollination. Here, we use the South African geophyteCyanella albato study how handedness of its mirror-image flowers is determined and elaborated during development. Inflorescences ofC. albaproduce flowers with a largely consistent handedness. However, we find that this handedness has no simple genetic basis, and individual plants can switch their predominant handedness between years. Rather, it is the direction of the phyllotactic spiral that determines floral handedness. Cellular analysis combined with biophysical modelling demonstrates that style deflection is driven by increased cell expansion in the adaxial carpel facing the next oldest flower compared to the other adaxial carpel. The more expanding carpel shows transcriptional signatures of increased auxin signaling compared to the less expanding one, and auxin application to the latter can reverse the orientation of style deflection. We propose that a recently described inherent LR auxin asymmetry in the initiating organs of spiral phyllotaxis determines handedness inC. alba, representing a conserved non-genetic mechanism for creating a stable floral polymorphism. This mechanism links chirality across different levels of plant development and exploits a developmental constraint in a core patterning process to produce morphological variation of ecological relevance.
Effect of environmental conditions on seed germination and seedling growth in
Cuscuta campestris
Authors: Nagao Koki , Takahashi Taku , Yokoyama Ryusuke
Published: June 2024

The dodder,
Cuscuta
, is an obligate parasitic plant that cannot survive without a host plant and causes major damage to crop yields. To know its growth characteristics before parasitism, we examined the effect of various environmental conditions on seed germination and seedling growth in
Cuscuta campestris
. As for the effect of light on germination, far-red light was rather preferable to red light and the reversible response of the seeds to red and far-red light was confirmed, implicating a phytochrome-mediated signaling opposite to that in many seed plants. Among amino acids, aspartic acid and alanine had a promotive effect and histidine had an inhibitory effect on germination. We further found that, in addition to gibberellic acid, methyl jasmonate was stimulatory to germination and shoot elongation. While 2,4-D extended the viability of trichomes around the root cap, kinetin induced the formation of scale leaves on the shoot and calli at the base of the shoot and the root tip. RT-PCR experiments confirmed that expression of a putative
RbcS
gene for photosynthesis showed no response to light but that of a
Phytochrome A
homolog was increased in the dark. Our results indicate that some of the molecular mechanisms to respond to light and hormone signals are uniquely modified in dodder seedlings, providing a clue for understanding the survival strategy of parasitic plants.
Sup4h5-L19 activation tagging line partially restores root hair growth inp4h5mutant by introducing small transcriptomic changes inArabidopsis thaliana
Authors: Urzúa Lehuedé Tomás , Núñez-Lillo Gerardo , Salgado Salter Juan , Acha Romina , Ibeas Miguel Angel , Meneses Claudio , Estevez José M.
Published: June 2024

An specific group of 2-oxoglutarate (2OG) dioxygenases named as Prolyl 4-Hydroxylases (P4H) produce trans-4-hydroxyproline (Hyp/O) from peptidyl-proline, catalyzing proline hydroxylation of cell wall glycoproteins EXT, AGPs, and HRGPs in plant cells, a crucial modification forO-glycosylation. Out of the Arabidopsis thaliana 13 P4Hs, P4H5 regulate root hair cell elongation and T-DNA insertionalp4h5mutant has arrested cell elongation and shortened root hairs. P4H5 selectively hydroxylates EXT proline units indicating that EXT proline hydroxylation as an essential modification for root hair growth. In this work, we isolate an activation-tagging line called Sup4h5-L19/p4h5(p4h5-L19) that partially suppressed root hair phenotype in thep4h5mutant background. The T-DNA insertion site was mapped by Thermal Asymmetric Interlaced PCR (TAIL-PCR) followed by PCR product sequencing and the T-DNA is inserted at the beginning of the sixth exon of the AT3G17750 gene, an uncharacterized cytosolic kinase. By analyzing expression changes and mutants analysis in this loci, no clear direct effect was detected. By RNA-seq analysis, it become clear thatp4h5-L19 may largely reverse the genetic alterations caused by thep4h5mutant in Wt Col-0, particularly at 10°C where there is an increase in root hair growth, with a total of 14 genes that have been activated and 83 genes that have been suppressed due to the enhancer of the activation tagging L19 inp4h5L19 compared top4h5. Among these genes, 3 of them, Tonoplast Intrinsic Proteins (TIPs), were identified to be root hair specific (TIP1;1, TIP2;2, and TIP2;3) and the corresponding mutants for two of them (TIP1;1 and TIP2;3) showed reduced root hair growth response at low temperature. This study unmasked new components of the root hair growth response at low temperature that works independently of theO-glycosyated EXTs in the cell walls.
Single-nucleus multiomic analysis of Beckwith-Wiedemann syndrome liver reveals PPARA signaling enrichment and metabolic dysfunction
Authors: Nirgude Snehal , Tichy Elisia D. , Liu Zhengfeng , Pradieu Rose D. , Byrne Mariah , Gil De Gomez Luis , Mamou Brandon , Bernt Kathrin M. , Yang Wenli , MacFarland Suzanne , Xie Michael , Kalish Jennifer M.
Published: June 2024

Beckwith-Wiedemann Syndrome (BWS) is an epigenetic overgrowth syndrome caused by methylation changes in the human 11p15 chromosomal locus. Patients with BWS exhibit tissue overgrowth, as well as an increased risk of childhood neoplasms in the liver and kidney. To understand the impact of these 11p15 changes, specifically in the liver, we performed single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) to generate paired, cell-type-specific transcriptional and chromatin accessibility profiles of both BWS-liver and nonBWS-liver nontumorous tissue. Our integrated RNA+ATACseq multiomic approach uncovered hepatocyte-specific enrichment and activation of the peroxisome proliferator-activated receptor α (PPARA) – a liver metabolic regulator. To confirm our findings, we utilized a BWS-induced pluripotent stem cell (iPSC) model, where cells were differentiated into hepatocytes. Our data demonstrates the dysregulation of lipid metabolism in BWS-liver, which coincided with observed upregulation of PPARA during hepatocyte differentiation. BWS liver cells exhibited decreased neutral lipids and increased fatty acid β-oxidation, relative to controls. We also observed increased reactive oxygen species (ROS) byproducts in the form of peroxidated lipids in BWS hepatocytes, which coincided with increased oxidative DNA damage. This study proposes a putative mechanism for overgrowth and cancer predisposition in BWS liver due to perturbed metabolism.
Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment
Authors: Smith Eric A. , Belote Rachel L. , Cruz Nelly M. , Moustafa Tarek E. , Becker Carly A. , Jiang Amanda , Alizada Shukran , Chan Tsz Yin , Seasor Tori A. , Balatico Michael , Cortes-Sanchez Emilio , Lum David H. , Hyngstrom John R. , Zeng Hanlin , Deacon Dekker C. , Grossmann Allie H. , White Richard M. , Zangle Thomas A. , Judson-Torres Robert L.
Published: June 2024

Acral melanoma (AM) is an aggressive melanoma variant that arises from palmar, plantar, and nail unit melanocytes. Compared to non-acral cutaneous melanoma (CM), AM is biologically distinct, has an equal incidence across genetic ancestries, typically presents in advanced stage disease, is less responsive to therapy, and has an overall worse prognosis. Independent analysis of published genomic and transcriptomic sequencing identified that receptor tyrosine kinase (RTK) ligands and adapter proteins are frequently amplified, translocated, and/or overexpressed in AM. To target these unique genetic changes, a zebrafish acral melanoma model was exposed to a panel of narrow and broad spectrum multi-RTK inhibitors, revealing that dual FGFR/VEGFR inhibitors decrease acral-analogous melanocyte proliferation and migration. The potent pan-FGFR/VEGFR inhibitor, Lenvatinib, uniformly induces tumor regression in AM patient-derived xenograft (PDX) tumors but only slows tumor growth in CM models. Unlike other multi-RTK inhibitors, Lenvatinib is not directly cytotoxic to dissociated AM PDX tumor cells and instead disrupts tumor architecture and vascular networks. Considering the great difficulty in establishing AM cell culture lines, these findings suggest that AM may be more sensitive to microenvironment perturbations than CM. In conclusion, dual FGFR/VEGFR inhibition may be a viable therapeutic strategy that targets the unique biology of AM.
Transformer-based modeling of Clonal Selection and Expression Dynamics (TraCSED) reveals resistance signatures in breast cancer
Authors: Maulding Nathan , Zou Jun , Zhou Wei , Metcalfe Ciara , Stuart Josh , Ye Xin , Hafner Marc
Published: June 2024

Understanding transcriptional heterogeneity in cancer cells and its implication for treatment response is critical to identify how resistance occurs and may be targeted. Such heterogeneity can be captured byin vitrostudies through clonal barcoding methods. We present TraCSED (Transformer-based modeling of Clonal Selection and Expression Dynamics), a dynamic deep learning approach for modeling clonal selection. Using single-cell gene expression and the fitness of barcoded clones, TraCSED identifies interpretable gene programs and the timepoints at which they are associated with clonal selection. When applied to cells treated with either giredestrant, an estrogen receptor (ER) antagonist and degrader, or palbociclib, a CDK4/6 inhibitor, time-dependent resistance pathways are revealed. For example, ER activity is associated with positive selection around day four under palbociclib treatment and this adaptive response can be suppressed by combining the drugs. Yet, in the combination treatment, one clone still emerged. Clustering based on partial least squares regression found that high baseline expression of both SNHG25 and SNCG genes was the primary marker of positive selection to co-treatment and thus potentially associated with innate resistance – an aspect that traditional differential analysis methods missed. In conclusion, TraCSED enables associating pathways with phenotypes in a time-dependent manner from scRNA-seq data.
High orientation and low delayed recall in the standardisation of the Spanish version of the Montreal Cognitive Assessment (MoCA) in elders of Peru
Authors: Bulgarelli Lucia , Gyr Emilia , Villanueva Jose , Mejía Koni , Mejía Claudia , Paredes Renato , Blumen Sheyla
Published: June 2024

INTRODUCTION

The elderly in Peru face healthcare barriers in detecting cognitive impairment and dementia due to a lack of validated tools. The Montreal Cognitive Assessment (MoCA) effectively detects early dementia, assessing visuo-spatial function, executive function, naming, memory, attention, language, abstraction, and orientation.

METHODS

This study aims to standardise the Spanish version of the MoCA for the elderly in Lima. The test was administered to 338 elders from three institutions: Municipality of San Miguel District, San José Obrero Polyclinic, and EDMECON. Regression-based normed scores were computed, adjusted for age and education.

RESULTS

Our results show high orientation scores and low delayed recall, highlighting cognitive strengths and weaknesses in our sample. Age and education significantly influenced cognitive performance, with education as the strongest predictor.

DISCUSSION

This study offers normative data for the Peruvian elderly, aiding the clinical use of MoCA in Peru. We discuss appropriate cut-off points and cultural sensitivity in the Peruvian context.
An international study to investigate and optimise the safety of discontinuing valproate in young men and women with epilepsy: protocol
Authors: Mbizvo Gashirai K. , Martin Glen P. , Sperrin Matthew , Bonnett Laura J. , Schofield Pieta , Buchan Iain , Lip Gregory Y.H. , Marson Anthony G.
Published: June 2024

Valproate is the most effective treatment for idiopathic generalised epilepsy. Currently, its use is restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk to men’s offspring, prompting recommendations to restrict use in everybody aged <55 years.

This study will evaluate mortality and morbidity risks associated with valproate withdrawal by emulating a hypothetical randomised-controlled trial (called a “target trial”) using retrospective observational data. The data will be drawn from ∼250m mainly US patients in the TriNetX repository and ∼60m UK patients in Clinical Practice Research Datalink (CPRD). These will be scanned for individuals aged 16–54 years with epilepsy and on valproate who either continued, switched to lamotrigine or levetiracetam, or discontinued valproate between 2015–2018, creating four groups. Randomisation to these groups will be emulated by baseline confounder adjustment using g-methods. Mortality and morbidity outcomes will be assessed and compared between groups over five years, employing time-to-first-event and recurrent events analyses. A causal prediction model will be developed from these data to aid in predicting the safest alternative antiseizure medications.

Together, these findings will optimise informed decision-making about valproate withdrawal and alternative treatment selection, providing immediate and vital information for patients, clinicians and regulators.
Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression: A protocol for a systematic review and meta-analysis
Authors: F Rodrigues Michele , Junkes Larissa , C Appolinario Jose , E Nardi Antonio
Published: June 2024

Background

Major Depressive Disorder is a global health issue that affects more than 300 million people worldwide, which is about 4.4% of the global population. Treatment usually consists of a combination of antidepressant medication and therapy. However, approximately 30% of individuals with Major Depressive Disorder experience a Treatment-Resistant Depression (a failure to respond to at least two antidepressants used in a regular dosage and time interval). Our research aims to investigate how effective Mindfulness-Based Cognitive Therapy is for individuals with Treatment-Resistant Depression.

Materials and Methods

We will conduct a thorough search for publications in MEDLINE, Embase, PsycINFO, Web of Science databases, and ClinicalTrials.gov. Additionally, we will manually review the reference lists of the included studies to find any other potentially relevant studies. There will be no restrictions on language or publication date. The quality of the included studies will be assessed independently using the Jadad scale (Oxford quality scoring system). To assess the certainty of the evidence, we will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. This study aims to determine the effectiveness and tolerability of Mindfulness-Based Cognitive Therapy as an intervention for Treatment-Resistant Depression.

Ethics and dissemination

Ethical approval is not necessary because individual patient data is not being collected. Our objective is to publish the systematic review in an open-access medical journal once the review process is completed.

Prospero registration ID

CRD42023411978. Registered on April 07, 2023.
Unveiling the gap of heart failure: a DATASUS study
Authors: Batista Vivian Cardoso , Vitorasso Renato Lima , Nogueira-Pileggi Vicky , Picoli Renato Mantelli , Bilevicius Elizabeth
Published: June 2024

Heart failure (HF) decompensation is the main cause of hospitalizations in developed countries. In Brazil, it represents the third general cause. Aiming to analyze the treatment journey for different types of HF in Brazil, the present study seeks to define a flowchart and clinical rationale that covers the procedures (and their respective frequency) in patients with HF in the Brazilian Unified Health System (SUS) included in DATASUS database. By doing so, the final objectives were: a) To identify potential patients with HF to present an estimate of the underreporting of the disease in the country; b) To describe the estimated mortality of potential patients with HF in Brazil. We used data from DATASUS, which encompasses information from the Brazilian Unified Health System (SUS). Specifically, we utilized the SUS-SIM (Mortality Information System) and SUS-SIA (Ambulatory Information System). Results: According to the data, we had a potential missing of patients with HF of 54,000 patients per year at diagnosis and 200,000 deaths that could lead to HF (both sexes). Considering the sensitivity analysis when there was a 20% underestimation in the number of potential HF cases, the underestimation rate of cases diagnosed with HF was 12%. We also found that when there was an underestimation of 40% in potential cases of death due to HF, there was an average underestimation of 41% in cases of death diagnosed as HF. the results highlight the importance of accurate diagnosis and a comprehensive approach to identifying potential cases of HF to improve the recording and management of this condition. Underestimation of these cases may have significant implications for public health and clinical management of HF emphasizing the need for strategies to increase early detection and adequate case recording. The next steps would be how much this underestimation impacts the public health in Brazil, particularly in terms of financial resources.
Refining the Allostatic Self-Efficacy Theory of Fatigue and Depression Using Causal Inference
Authors: Hess Alexander J. , von Werder Dina , Harrison Olivia K. , Heinzle Jakob , Stephan Klaas Enno
Published: June 2024

Allostatic self-efficacy (ASE) represents a computational theory of fatigue and depression. In brief, it postulates that (i) fatigue is a feeling state triggered by a metacognitive diagnosis of loss of control over bodily states (persistently elevated interoceptive surprise); and that (ii) generalisation of low self-efficacy beliefs beyond bodily control induces depression. Here, we convert ASE theory into a structural causal model (SCM). This allows for identification of empirically testable hypotheses regarding casual relationships between variables of interest. We use conditional independence tests on questionnaire data from healthy volunteers (N=60) to identify contradictions to the proposed SCM. Moreover, we estimate two causal effects proposed by ASE theory using three different methods.

Our analyses suggest that, in healthy volunteers, the data are not fully compatible with the proposed SCM. We therefore refine the SCM and present an updated version for future research. Second, we confirm the predicted negative average causal effect from metacognition of allostatic control to fatigue across all three different methods of estimation. Our study represents an initial attempt to refine and formalise ASE theory using methods from causal inference. Our results confirm key predictions from the ASE theory but also suggest revisions which require empirical verification in future studies.