bluuebunny/crossref_metadata_2025 huggingface dataset:
An Atypical Presentation of Ischemic Stroke in a Middle-Aged Adult
Authors: Buck Martha
Published: August 2024

Stroke-like symptoms are a common complaint in the emergency department; however, signs of an acute cerebrovascular event in a patient under the age of 50 can be both alarming and unexpected. In this case, a 41-year-old male presented to the emergency department with vague symptoms of intermittent weakness and paresthesias for 4 days. Originally deemed a “stroke code” in the field, the patient was immediately transferred to the computerized tomography scanner. The patient was later found to have a right-sided internal carotid dissection and subsequent right parietal lobe ischemic infarcts. This article highlights the need to maintain a high suspicion for acute cerebrovascular events, even in atypical presentations. The key features of caring for a patient experiencing carotid dissection, as well as their expected prognosis and care course, are also expounded upon. Early recognition of stroke-like symptoms in young, otherwise healthy, patients is critical to providing the needed care in a timely manner and to preserve future function and quality of life.
The Resurgence of Measles
Authors: Gooch Michael D.
Published: August 2024

Measles, or rubeola, remains a highly contagious infectious disease with a concerning resurgence in the United States. Despite previous control efforts, the number of reported cases continues to rise, surpassing the total for the previous year in just the first quarter of 2024 (CDC, 2024a). Emergency nurse practitioners and other emergency clinicians are likely to encounter patients presenting with concerns of or exposure to measles. However, given the low frequency of cases in the past, many emergency clinicians have likely not previously encountered measles, making identification more challenging. Early recognition and isolation are paramount in containing the spread of this virus and mitigating potential complications. This article aims to provide a review of measles, covering its pathophysiology, clinical presentations, and recommended management strategies for suspected or confirmed cases in emergency care settings.
Emergency Department Length of Stay
Authors: Bennage Johnette K. , Ford Cassandra D. , Ezemenaka Christina J. , Persing Tamara F.
Published: August 2024

Objective:

This quality improvement initiative was conducted to determine if a provider in triage and split flow model could decrease the length of stay (LOS) of discharged patients seen in a community hospital emergency department (ED).

Background:

Extended LOSs within the ED lead to delays in the care of patients, increase the number of patients who leave without being seen by a provider, decrease patient satisfaction, and cause a loss of revenue for health care organizations. Using a provider in triage and a split flow model, where patients can be seen and dispositioned without delays, can improve ED throughput and decrease the overall LOS.

Methods:

Through a structured, interdisciplinary approach using the Plan-Do-Study-Act Shewhart Cycle of Process Improvement, a provider was placed in triage, and an interior waiting room was used to evaluate emergency severity index level 3 and 4 patients to expedite diagnostic testing and perform procedures. This model allowed lower acuity patients to be cared for separately from higher acuity patients, who were being treated in the main ED. In addition, the median arrival to provider, arrival to bed, and LOS from arrival to departure of discharged patients were compared to the current departmental processes.

Results:

There was a significant improvement in the LOS of discharged patients and the time of arrival to triage, arrival to bed, and arrival to provider using a provider in triage and a split flow model compared to the current intake.

Conclusion:

Implementation of a provider in triage and a split flow model can demonstrate a decrease in the LOS of discharged patients along with other ED metrics and improve efficiencies in patient care within a community hospital.
Dream of the Endless
Authors: Bailey Abby M. , Weant Kyle A.
Published: August 2024

Procedural sedation and analgesia is an essential activity in the emergency department for managing pain and anxiety during a variety of medical procedures. Various pharmacotherapy options, including opioid analgesics, antiemetics, anticholinergics, sedatives, and ketamine have been utilized, all with their unique efficacy and safety profiles. This review highlights the challenges associated with using certain agents and discusses emerging trends such as the use of newer synthetic opioids and the expanding use of dexmedetomidine. Overall, the selection of the optimal agents for procedural sedation and analgesia should be guided based on the unique characteristics of each agent tailored to the needs of the specific procedure, along with consideration for individual patient characteristics.
Articulatory-based Phonemic Paraphasia in Conduction Aphasia: A Dysfunction in Phoneme-to-Articulation Conversion Uncovered Through Crossed Aphasia
Authors: Kawashima Hiroaki , Funayama Michitaka , Inaba Yoshie , Baba Mikoto
Published: August 2024

Phonemic paraphasia, a common characteristic of conduction aphasia, has traditionally been attributed to phonological representation dysfunction. An alternative hypothesis posits that phonemic paraphasia arises from difficulty converting phonemes into their corresponding articulatory maneuvers. However, detailed case studies supporting this theory have been lacking. In this report, we present the case of a 61-year-old right-handed man with right temporo-parietal infarction who exhibited crossed aphasia characterized by typical conduction aphasia symptoms (eg, relatively fluent speech with intact comprehension, frequent phonemic paraphasia, and pronounced difficulties in oral repetition) in the absence of distorted articulation, syllable segmentation, and prosody impairment. Despite the frequent occurrence of phonemic paraphasia and articulatory challenges, our patient’s phonological representations remained relatively intact. His phonemic paraphasia was often self-corrected to produce correct responses, a feature known as conduit d’approche. During the oral repetition of individual mora (ie, the smallest unit of speech in Japanese), we observed that the patient consistently traced the corresponding Hiragana phonetic symbol accurately, despite his difficulties in articulation. We substantiated this phenomenon through objective assessment and posit that it resulted from an unusual separation of language functions in crossed aphasia—specifically, a disconnection between phonological representations in the right temporo-parietal cortex and speech articulation engrams in the left hemisphere. In this case of conduction aphasia, articulatory-based phonemic paraphasia may be viewed as an inability to convert phonemes into the appropriate articulatory maneuvers rather than as phonological representation dysfunction or apraxia of speech.
A case of pleural Mycobacterium tuberculosis infection with reversion of Quantiferon Gold Plus results from positive to negative.
Authors: Goire Namraj , Suchard Melinda , Barling Andrew , Fernando Ruchira , Dreyer Linda , Mahony Andrew
Published: August 2024

Introduction
Mycobacterium tuberculosis  continues to have a high mortality and morbidity burden globally. IGRA such as Quantiferon Gold Plus aid in diagnosis of latent TB but diagnosis of pleural TB remains challenging. We present a case of active pleural MTB infection with reversion of IGRA from positive to negative, and negative Xpert MTB/RIF Ultra PCR results from pleural biopsy tissues.
Case
A 52-year-old male presented in 2022 with a two-week history of pleuritic chest pain associated with modest elevation in inflammatory markers. The patient had had a positive QFG-Plus result in 2018, however QFG-Plus during this admission was negative. CTPA and needle thoracocentesis showed an exudative left pleural effusion with predominant lymphocytes. The patient’s symptoms failed to resolve with empiric antimicrobial therapy for community-acquired pneumonia.  Broncho-Alveolar Lavage as well as biopsies of pleural tissues via video-assisted thoracoscopic surgery from the left lower lobe yielded negative results on routine microbiological culture as well as Xpert Ultra PCR. Growth of AFB was noted from mycobacterial cultures of pleural tissues which was identified as MTB.
Conclusion
Despite significant technological advances, microbiological diagnosis of MTB infections remains challenging. We document QFG-Plus reversion during development from latent to active pleural TB. Decline in the ability of CD4+ and CD8+ T cells to produce interferon gamma in response to TB antigens (ESAT-6 and CFP-10) was likely associated with loss of host control of latent MTB. This case serves as a reminder that despite exhaustive testing with state-of-art diagnostic platforms, MTB  can still elude discovery.
Next-generation sequencing of pIJ101-based Streptomyces-E. coli shuttle vectors
Authors: Brown Katelyn Victoria , Nybo Stephen Eric
Published: August 2024

High-copy number plasmids are indispensable tools for gene overexpression studies in prokaryotes to engineer pathways or probe phenotypes of interest. Industrially relevant actinomycetes are interested in producing keratolytic enzymes and various biologically active natural products. Within the Actinomycetota class, Streptomyces-Escherichia coli shuttle vectors based on the SCP2* and pIJ101 incompatibility groups are widely employed for molecular cloning and gene expression studies. Here, the sequences of two commonly used pIJ101-based Streptomyces-E. coli shuttle vectors, pEM4, and pUWL201, were determined using next-generation sequencing and mapping. These plasmids drive the expression of heterologous genes using the constitutive ermE*p promoter. pEM4 was found to be 8.3 kbp long, containing genes encoding β-lactamase, thiostrepton resistance, the lacZɑ fragment, an E. coli pUC19 origin of replication, and the Streptomyces pIJ101 origin of replication. pUWL201 was found to be 6.78 kbp long, containing genes encoding β-lactamase, thiostrepton resistance, the lacZɑ fragment, an E. coli pUC19 origin of replication, and the Streptomyces pIJ101 origin of replication. Interestingly, the sequences for both pEM4 and pUWL201 exceed their previously reported size by 1.1 kbp and 0.4 kbp, respectively. This report updates the literature with the corrected sequences for these expression vectors, ensuring their compatibility with modern synthetic biology cloning methodologies.
Whole-genome sequencing of Western Canadian Borrelia spp. collected from diverse tick and animal hosts reveals short-lived local genotypes interspersed with longer-lived continental genotypes
Authors: Russell Jennifer N. , Lee Min-Kuang , Uyaguari-Diaz Miguel I. , Sies Ashton N. , Suchan Danae M. , Hsiao William , Fraser Erin , Morshed Muhammad G. , Cameron Andrew D. S.
Published: August 2024

Changing climates are allowing the geographic expansion of ticks and their animal hosts, increasing the risk of Borrelia-caused zoonoses in Canada. However, little is known about the genomic diversity of Borrelia from the west of the Canadian Rockies and from the tick vectors Ixodes pacificus, Ixodes auritulus and Ixodes angustus. Here, we report the whole-genome shotgun sequences of 51 Borrelia isolates from multiple tick species collected on a range of animal hosts between 1993 and 2016, located primarily in coastal British Columbia. The bacterial isolates represented three different species from the Lyme disease-causing Borrelia burgdorferi sensu lato genospecies complex [Borrelia burgdorferi sensu stricto (n=47), Borrelia americana (n=3) and Borrelia bissettiae (n=1)]. The traditional eight-gene multi-locus sequence typing (MLST) strategy was applied to facilitate comparisons across studies. This identified 13 known Borrelia sequence types (STs), established 6 new STs, and assigned 5 novel types to the nearest sequence types. B. burgdorferi s. s. isolates were further differentiated into ten ospC types, plus one novel ospC with less than 92 % nucleotide identity to all previously defined ospC types. The MLST types resampled over extended time periods belonged to previously described STs that are distributed across North America. The most geographically widespread ST, ST.12, was isolated from all three tick species. Conversely, new B. burgdorferi s. s. STs from Vancouver Island and the Vancouver region were only detected for short periods, revealing a surprising transience in space, time and host tick species, possibly due to displacement by longer-lived genotypes that expanded across North America.

This article contains data hosted by Microreact.
Distinguishing clinical and genetic risk factors for suicidal ideation and behavior in a diverse hospital population
Authors: Colbert Sarah M.C. , Lepow Lauren , Fennessy Brian , Iwata Nakao , Ikeda Masashi , Saito Takeo , Terao Chikashi , Preuss Michael , Pathak Jyotishman , Mann J. John , Coon Hilary , Mullins Niamh
Published: August 2024

Suicidal ideation (SI) and behavior (SB) are major public health concerns, but risk factors for their development and progression are poorly understood. We used ICD codes and a natural language processing algorithm to identify individuals in a hospital biobank with SI-only, SB, and controls without either. We compared the profiles of SB and SI-only patients to controls, and each other, using phenome-wide association studies (PheWAS) and polygenic risk scores (PRS). PheWAS identified many risk factors for SB and SI-only, plus specific psychiatric disorders which may be involved in progression from SI-only to SB. PRS for suicide attempt were only associated with SB, and even after accounting for psychiatric disorder PRS. SI PRS were only associated with SI-only, although not after accounting for psychiatric disorder PRS. These findings advance understanding of distinct genetic and clinical risk factors for SB and SI-only, which will aid in early detection and intervention efforts.
Imaging protocol suggested by large language model depends on language: preliminary experiments using GPT-4
Authors: Suzuki Kazufumi , Abe Kayoko , Sakai Shuji
Published: August 2024

Purpose

This study aimed to evaluate the potential of GPT-4, a large language model, in assisting radiologists to determine brain magnetic resonance imaging (MRI) protocols.

Methods

We used brain MRI protocols from a specific hospital, covering 20 diseases or examination purposes, excluding brain tumor protocols. GPT-4 was given system prompts to add one MRI sequence for the basic brain MRI protocol and disease names were input as user prompts. The model’s suggestions were evaluated by two radiologists with over 20 years of relevant experience. Suggestions were scored based on their alignment with the hospital’s protocol as follows: 0 for inappropriate, 1 for acceptable but nonmatching, and 2 for matching the protocol. The experiment was conducted in both Japanese and English to compare GPT-4’s performance in different languages.

Results

GPT-4 scored 27/40 points in English and 28/40 points in Japanese. GPT-4 gave inappropriate suggestions for Moyamoya disease and neuromyelitis optica in both languages and cerebral infarction in Japanese. For the other protocols, the suggested sequences were either appropriate or better. The suggestions in English differed from those in Japanese for seven protocols.

Conclusion

GPT-4 can suggest appropriate MRI sequences for each disease in addition to the standard brain MRI protocol. GPT-4’s output is language-dependent and suggests brain MRI protocols tailored to specific regions and domains.
LLIN Evaluation in Uganda Project (LLINEUP2) – Effect of long-lasting insecticidal nets (LLINs) treated with pyrethroid plus pyriproxyfen vs LLINs treated with pyrethroid plus piperonyl butoxide in Uganda: a cluster-randomised trial
Authors: Gonahasa Samuel , Namuganga Jane F , Nassali Martha J , Maiteki-Sebuguzi Catherine , Nabende Isaiah , Epstein Adrienne , Snyman Katherine , Nankabirwa Joaniter I , Opigo Jimmy , Donnelly Martin J , Dorsey Grant , Kamya Moses R , Staedke Sarah G
Published: August 2024

Background

We embedded a pragmatic, cluster-randomised trial into Uganda’s national campaign to distribute long-lasting insecticidal nets (LLINs) in 2020–2021, comparing LLINs treated with pyrethroids plus the synergist piperonyl butoxide (PBO), to LLINs treated with pyrethroids plus pyriproxyfen, an insect growth regulator.

Methods

Target communities surrounding public health facilities (clusters, n=64), covering 32 high-burden districts not receiving indoor residual spraying, were included. Clusters were randomised 1:1 in blocks of two by district to receive: (1) pyrethroid-PBO LLINs (PermaNet 3.0, n=32) or (2) pyrethroid-pyriproxyfen LLINs (Royal Guard, n=32). LLINs were delivered from 7 November 2020 to 26 March 2021 and malaria outcome data were collected until 31 March 2023. Estimates of malaria incidence in residents of all ages (the primary outcome) were generated for each cluster from enhanced health facility surveillance data. At 12- (24 November 2021 to 1 April 2022) and 24-months (23 November 2022 to 21 March 2023) post-LLIN distribution, cross-sectional community surveys were conducted in randomly selected households (at least 50 per cluster, 3,200 per survey).

Findings

In the two years following LLIN distribution, 186,364 episodes of malaria were diagnosed in cluster residents during 398,931 person-years of follow-up. Malaria incidence after 24-months was lower than at baseline in both arms (pyrethroid-PBO: 465 vs 676 episodes per 1000 person-years; pyrethroid-pyriproxyfen: 469 vs 674 episodes per 1000 person-years); but the difference between the arms was not statistically significant (incidence rate ratio 1.06, 95% confidence interval [CI] 0.91– 1.22, p=0.47). Two years post-distribution, ownership of at least one LLIN for every two household residents was low in both arms (41.1% pyrethroid-PBO vs 38.6% pyrethroid-pyriproxyfen). Parasite prevalence in children aged 2-10 years was no different between the arms in either survey and similar results were observed for prevalence of anaemia in children aged 2-4 years.

Interpretation

The effectiveness of pyrethroid-PBO LLINs and pyrethroid-pyriproxyfen LLINs was no different in Uganda, but two years after mass distribution, LLIN coverage was inadequate.

Funding

US National Institutes for Health, Bill and Melinda Gates Foundation

Trial registration

NCT04566510. Registered 28 September 2020,https://clinicaltrials.gov/ct2/show/NCT04566510
An axis of genetic heterogeneity in autism is indexed by age at diagnosis and is associated with varying developmental and mental health profiles
Authors: Zhang Xinhe , Grove Jakob , Gu Yuanjun , Buus Cornelia K. , Nielsen Lea K. , Neufeld Sharon A.S. , Koko Mahmoud , Malawsky Daniel S , Wade Emma , Verhoef Ellen , Gui Anna , Hegemann Laura ,   APEX consortium,   iPSYCH Autism Consortium,   PGC-PTSD Consortium, Geschwind Daniel H. , Wray Naomi R. , Havdahl Alexandra , Ronald Angelica , Pourcain Beate St. , Robinson Elise B. , Bourgeron Thomas , Baron-Cohen Simon , Børglum Anders D. , Martin Hilary C. , Warrier Varun
Published: August 2024

There is growing recognition that earliest signs of autism need not clearly manifest in the first three years of life. To what extent is this variation in developmental trajectories associated with age at autism diagnosis? Does the genetic profile of autism vary with age at autism diagnosis? Using longitudinal data from four birth cohorts, we demonstrate that two different trajectories of socio-emotional behaviours are associated with age at diagnosis. We further demonstrate that the age at autism diagnosis is partly heritable (h2SNP= 0.12, s.e.m = 0.01), and is associated with two moderately correlated (rg= 0.38, s.e.m = 0.07) autism polygenic factors. One of these factors is associated with earlier diagnosis of autism, lower social and communication abilities in early childhood. The second factor is associated with later autism diagnosis, increased socio-emotional difficulties in adolescence, and has moderate to high positive genetic correlations with Attention-Deficit/Hyperactivity Disorder, mental health conditions, and trauma. Overall, our research identifies an axis of heterogeneity in autism, indexed by age at diagnosis, which partly explains heterogeneity in autism and the profiles of co-occurring neurodevelopmental and mental health profiles. Our findings have important implications for how we conceptualise autism and provide one model to explain some of the diversity within autism.
Sex Differences in Colonic Mucosal Microbiome of Irritable Bowel Syndrome Patients Compared to Healthy Controls
Authors: Mahurkar-Joshi Swapna , Shera Simer , Labus Jennifer , Dong Tien S , Jacobs Jonathan P , Chang Lin
Published: August 2024

Background: Irritable bowel syndrome (IBS) is a female-predominant disorder of brain-gut interactions. Our previous study on colonic mucosal microbiota demonstrated significant differences between IBS bowel habit subtypes and showed that gut microbiota is associated with abdominal pain in IBS patients. However, there is no consensus on sex-related differences in mucosal microbiota in IBS compared to healthy controls (HC). We aimed to identify sex-related differences in the mucosal microbes associated with IBS. Methods: Sigmoid mucosal biopsies were obtained from 97 Rome+ IBS patients and 54 healthy controls (HC). Mucosal microbiome was characterized using 16S rRNA sequencing and analyzed and general linear models were used to test group differences between IBS diagnosis and sex. Sex-specific relationships between mucosal microbiome and IBS symptoms were assessed using sparse partial least squares (sPLS) regression. Results: Beta diversity was significantly different between men and women overall (p=.03) but not within IBS or HC. IBS women showed lower abundance of Catenibacterium and Ruminoclstridium_9 and increased abundance of Bacteroides, Escherichia/Shigella, Lachnoclostridium and Ruminococcaceae compared to men with IBS (p<0.05). However, healthy women had a lower abundance of six distinct genera compared to healthy men. In women, higher IBS symptoms were associated with an increased abundance of bacteria including prevotella_9, and paraprevotella, however, in men, IBS symptoms were associated with increased abundances of genera such as Dialister. Interestingly, increased abundance of Desulfovibrio was associated with higher symptoms in women but lower symptoms in men. Conclusion: There are distinct sex-related differences in the mucosal microbiome between IBS and healthy participants supporting the importance of studying sex-specific mechanisms in IBS pathophysiology.
Elevated remnant cholesterol improves prognosis of patients with ischemic stroke and malnutrition: a cohort-based study
Authors: Niu Huicong , Wang Yong , Yang Ning , Chu Min , Mao Xueyu , Wang Daosheng , Zhao Jing
Published: August 2024

Background

Aggressive lipid-lowering therapy is recommended for patients with ischemic stroke; however, lipid paradox has been reported in several clinical studies. The mechanism of lipid paradox remains uncertain, and nutrition maybe one explanation. In this prospective cohort study, we explored the associations between baseline remnant cholesterol (RC) concentrations and clinical outcomes in patients with ischemic stroke, stratified by nutritional status.

Materials and Methods

A total of 5257 patients with ischemic stroke were recruited for analysis. The Controlling Nutritional Status (CONUT) score was utilized to investigate the risk of malnutrition. Individuals were classified into 4 groups based on their CONUT score. Poor outcomes and all-cause mortality were compared among patients with varied nutritional status and RC levels.

Results

Patients with moderate-severe malnutrition had the highest incidences of in-hospital complications, including pulmonary infection, renal dysfunction, and hemorrhagic transformation, and the highest rates of poor outcomes (61.3%,P<0.001) and all-cause mortality (32.8%,P< 0.001) during the 3-month follow-up period. Baseline higher RC level was an independent protective factor of adverse clinical outcomes for patients with any degree of malnutrition, which was not observed in patients without malnutrition. In addition, compared with the moderate-severe malnourished with RC <0.471 mmol/L, the adjusted ORs for poor outcomes and all-cause mortality were 0.805 (0.450–1.438) and 0.898 (0.502-1.607) for participants with 0.471-0.632 mmol/L, 0.259 (0.095-0.704) and 0.222 (0.061-0.810) for 0.633-0.868 mmol/L, and 0.160 (0.037–0.689) and 0.202 (0.042-0.967) for ≥ 0.869 mmol/L, prospectively.

Conclusion

Lipid paradox was only observed in the malnourished patients with ischemic stroke. Strict lipid reduction therapy is still recommended for patients with ischemic stroke and good nutritional status. However, when treating patients at any risk of malnutrition, the improvement of nutritional status may be more crucial than aggressive lipid control.
Deciphering octoploid strawberry evolution with serial LTR similarity matrices for subgenome partition
Authors: Lyu Haomin , Ou Shujun , Yim Won Cheol , Yu Qingyi
Published: August 2024

Polyploidization has been recognized as a major force in plant evolution. With the continuous progress in sequencing technologies and genome assembly algorithms, high-quality chromosome-level assemblies of polyploid genomes have become increasingly attainable. However, accurately delineating these assemblies into subgenomes remains a challenging task, especially in case where known diploid ancestors are absent. In this study, we introduce a novel approach that leverages long terminal repeat retrotransposons (LTR-RTs) coupled with the Serial Similarity Matrix (SSM) method to assign genome assemblies to subgenomes, particularly beneficial for those without known diploid progenitor genomes. The SSM method helps identify subgenome-specific LTRs and facilitates the inference of the timing of allopolyploidization events. We validated the efficacy of the SSM approach using well-studied allopolyploidy genomes,Eragrostis tefandGossypium hirsutum, alongside an artificially created allotetraploid genome by merging two closely related diploid species,Glycine maxandG. soja. Our results demonstrated the robustness of the method and its effectiveness in assigning chromosomes to subgenomes. We then applied the SSM method to the octoploid strawberry genome. Our analysis revealed three allopolyploidization events in the evolutionary trajectory of the octoploid strawberry genome, shedding light on the evolutionary process of the origin of the octoploid strawberry genome and enhancing our understanding of allopolyploidization in this complex species.
Leveraging microtopography to pattern multi-oriented muscle actuators
Authors: Rossy Tamara , Schwendeman Laura , Bawa Maheera , Umashankar Pavankumar , Raman Ritu
Published: August 2024

Engineering skeletal muscle tissue with precisely defined alignment is of significant importance for applications ranging from drug screening to biohybrid robotics. Aligning 2D contractile muscle monolayers, which are compatible with high-content imaging and can be deployed in planar soft robots, typically require micropatterned cues. However, current protocols for integrating microscale topographical features in extracellular matrix hydrogels require expensive microfabrication equipment and multi-step procedures involving error-prone manual handling steps. To address this challenge, we present STAMP (Simple Templating of Actuators via Micro-topographical Patterning), an easily accessible and cost-effective one-step method to pattern microtopography of various sizes and configurations on the surface of hydrogels using reusable 3D printed stamps. We demonstrate that STAMP enables precisely controlling the alignment of mouse and human skeletal muscle fibers, and thus their force-generating axes, without impacting their maturation or function. To showcase the versatility of our technique, we designed a planar soft robot inspired by the iris, which leverages spatially segregated regions of concentric and radial muscle fibers to control pupil dilation. Optogenetic skeletal muscle fibers grown on a STAMPed iris substrates formed a multi-oriented actuator, and selective light stimulation of the radial and concentric fibers was used to control the function of the iris, including pupil constriction. Computational modeling of the biohybrid robot as an active bilayer matched experimental outcomes, showcase the robustness of our method of designing, fabricating, and testing planar biohybrid robots capable of complex multi-degree-of-freedom motion.
Violence against women and children in Yemen: A mixed-methods systematic review
Authors: Shreedhar Samana , Arvind Chavan Sayali , Al-Zumair Marwah , Naccache Mirna , Shreedhar Priya , Maxwell Lauren
Published: August 2024

Violence against women and children (VAWC) is a significant health and human rights issue closely tied to multiple Sustainable Development Goals. While VAWC is prevalent in all countries, the severity and incidence of VAWC increase during wars, natural disasters, economic crises, and pandemics, all of which have affected Yemen in recent years. This systematic review synthesizes evidence from qualitative and quantitative studies on the types, prevalence, perpetrators of, and risk factors for VAWC in Yemen. Before initiating the search, the protocol and search strategy were registered to PROSPERO (CRD42021237855). We systematically searched four biomedical databases and grey literature sources and used reverse snowball sampling to identify eligible studies. The 31 studies included in the analysis depicted a range of forms of VAWC, encompassing honor violence, female genital mutilation and cutting, early and very early marriage, tourist marriage, family and intimate partner violence, and gender inequities in access to food, education, and medical care. Included studies reported a high prevalence of many forms of violence, including corporal punishment in schools and intimate partner violence. We reviewed study quality and how studies addressed ethical concerns in VAWC-related research. We found that several studies did not report ethics review or interviewer training and no studies discussed safety planning or addressing the mental health needs of participants in VAWC research. This systematic review provides a much-needed synthesis of existing research on VAWC in Yemen. Since the start of the 2014 war, Yemen has become the world's largest humanitarian crisis, with the highest rate of maternal mortality and gender inequality in the world. We only identified one study initiated after the recent war in Yemen. This deficiency represents a missed opportunity to understand how the ongoing war has reversed prior gains in reducing the prevalence of child and very early child marriage and introduced new forms of gender-based violence, including tourist marriage.
NXT2 is the key player for nuclear RNA export in the human testis and critical for spermatogenesis
Authors: Dicke Ann-Kristin , Ahmedani Ammar , Ma Lin , van der Heijden Godfried W. , Koser Sophie A. , Krallmann Claudia , Kalyon Oguzhan , Xavier Miguel J. , Veltman Joris A. , Kliesch Sabine , Neuhaus Nina , Kotaja Noora , Tüttelmann Frank , Stallmeyer Birgit
Published: August 2024

In eukaryotes, the nucleocytoplasmic export of bulk poly(A)+-mRNAs through the nuclear pore complex is mediated by the ubiquitously expressed NXT1-NXF1 heterodimer. In humans,NXT1has an X-chromosomal paralog,NXT2,which exhibits testis-enriched expression, suggesting a role in spermatogenesis. Here, we report thein vivointeraction of NXT2 with crucial components of the nuclear export machinery, including NXF1, the testis-specific NXF1 paralogs NXF2 and NXF3, and the nuclear pore complex proteins NUP93 and NUP214. Further, NXT2’s NTF2-like domain mediates binding to NXF2 and NXF3. By identifying infertile men with loss-of-function variants inNXT2andNXF3, we link the impaired NXT2-NXF activity to disturbed germ cell development. The predominant absence of germ cells in men with NXT2 deficiency indicates its critical function already during fetal or first steps of germ cell development. In contrast, loss of NXF3 affects later stages of spermatogenesis resulting in quantitatively and qualitatively impaired sperm production.
Microvascular Metrics on Diabetic Retinopathy: Insights from a Meta-Analysis of Diabetic Eye Images from Real-World Data
Authors: Cuscó Cristina , Esteve Pau , Almazán-Moga Ana , Fernández-Carneado Jimena , Ponsati Berta
Published: August 2024

Objective

To quantify microvascular lesions in a large Real-World Data (RWD) set, based on single central retinal fundus images from different origins, with the aim of validating its use as a precision tool for classifying Diabetic Retinopathy (DR) severity.

Design

Retrospective meta-analysis across multiple fundus image datasets.

Sample size

The study analyzed 2,340 retinal fundus images from diabetic patients across four diverse RWD international datasets, including populations from Spain, India, China and the US.

Intervention

The quantification of specific microvascular lesions: microaneurysms (MAs), hemorrhages (Hmas) and hard exudates (HEs) using advanced automated image analysis techniques on central retinal images to validate reliable metrics for DR severity assessment. The images were pre-classified in the DR severity levels as defined by the International Clinical Diabetic Retinopathy (ICDR) scale.

Main Outcome Measures

The primary variables measured were the number of MAs, Hmas, red lesions (RLs) and HEs. These counts were related with DR severity levels using statistical methods to validate the relationship between lesion counts and disease severity.

Results

The analysis revealed a robust and statistically significant increase (p<0.001) in the number of microvascular lesions and the DR severity across all datasets. Tight data distributions were reported for MAs, Hmas and RLs, supporting the reliability of lesion quantification for accurately assessing DR severity. HEs also followed a similar pattern, but with a broader dispersion of data. Data used in this study are consistent with the definition of the DR severity levels established by the ICDR guidelines.

Conclusions

The statistically significant increase in the number of microvascular lesions across DR severity validate the use of lesion quantification in a single central retinal field as a key biomarker for disease classification and assessment. This quantification method demonstrates an improvement over traditional assessment scales, providing a quantitative metric that enhances the precision of disease classification and patient monitoring. The inclusion of a numerical component allows for the detection of subtle variations within the same severity level, offering a deeper understanding of disease progression. The consistency of results across diverse datasets not only confirms the method’s reliability but also its applicability in a global healthcare setting.
Migraine and Early-onset Ischemic Stroke: A Mendelian Randomization Study
Authors: Niu Peng-Peng , Zhang Rui , Li Shuo , Li Yu-Sheng
Published: August 2024

Objective

Through the utilization of the data specifically related to early-onset ischemic stroke, we aimed to investigate the causal effects of migraine and its subtypes on the risk of early-onset ischemic stroke using the two-sample Mendelian randomization method.

Methods

Genetic instrumental variables were acquired from two sources with the largest sample sizes available. Summary data for early-onset ischemic stroke was acquired from a study encompassing individuals aged 18 to 59 years, comprising 16,730 cases and 599,237 non-stroke controls. The random-effects inverse variance weighted method was used as the primary analysis approach.

Results

The Mendelian randomization analysis revealed no association between overall migraine and migraine without aura with the risk of early-onset ischemic stroke. However, migraine with aura showed a suggestive association with an elevated risk of early-onset ischemic stroke, with odds ratios of 1.114 (95% confidence interval = 1.005 to 1.236, p-value = 0.040) and 1.062 (95% confidence interval = 1.002 to 1.126, p-value = 0.042) based on instruments from two independent sources. The odds ratio was 1.074 (95% confidence interval = 1.022 to 1.130, p-value = 0.005) based on instruments from both two sources. No evidence of heterogeneity or horizontal pleiotropy was found. Furthermore, a positive genetic correlation was found between migraine with aura and early-onset ischemic stroke (genetic correlation = 0.208, 95% confidence interval = 0.038 to 0.377, p-value = 0.016). By contrast, migraine with aura was not related to ischemic stroke of all adults.

Conclusion

This study provides evidence of a causal relationship between migraine with aura and the risk of early-onset ischemic stroke.
Decline in striatal binding ratio associated with accelerated decline in performance on Symbol Digit Modality but not MoCA in Parkinson’s disease psychosis
Authors: Pisani Sara , Velayudhan Latha , Aarsland Dag , Chaudhuri K. Ray , Ballard Clive , ffytche Dominic , Bhattacharyya Sagnik
Published: August 2024

Background

Cognitive deficits have been reported in Parkinson’s Disease psychosis (PDP). Reduced dopamine transporter (DAT) binding ratio has also been associated with PDP. However, it remains unclear whether DAT striatal binding ratio (SBR) may contribute to worsening cognitive performance in PDP. Here, we examined this using data from the Parkinson’s Progression Markers Initiative study.

Methods

We analysed data from 408 PD patients, from baseline to year 4 follow up, and classified patients into PD with (PDP) and without psychosis (PDnP). DAT SBR was available from DaTSCAN imaging with123I-FP-CIT-SPECT. We examined all cognitive measures assessed at each time point, socio-demographics, neuropsychiatric and PD-specific symptoms were entered as covariates of interest.

Results

PDP patients had lower DAT SBR compared to PDnP patients (b=-0.092,p=0.035) which remained significant after controlling for age, sex, and ethnicity. PDP patients also reported worse trajectory of task performance on MoCA (b=-0.238,p=0.001) and Symbol Digit Modality (b=-0.534,p=0.016) across four years compared to PDnP patients. Worsening of MoCA scores in PDP was independent of DAT SBR decline (interaction group * study years, b=-0.284,p=0.016; three-way interaction group*study years*DAT SBR, b=0.127,p=0.225). However, declining performance in Symbol Digit Modality was significantly associated with the decline in DAT SBR (three-way interaction group*study years*DAT SBR, b=0.683,p=0.028).

Conclusion

Overall, longitudinal decline in striatal presynaptic dopamine function may underlie the greater longitudinal decline in performance in the symbol digit modality task that engages processing speed, associative learning and working memory in PD psychosis, whilst declining performance on MoCA seems unrelated to it. Whether striatal presynaptic dopamine changes explain accelerated longitudinal decline in other cognitive domains in people with PDP remains to be tested.
Propranolol reduces Parkinson’s tremor and inhibits tremor-related activity in the motor cortex: a placebo-controlled crossover trial
Authors: van der Heide Anouk , Wessel Maaike , Papadopetraki Danae , Geurts Dirk E.M. , van Prooije Teije H. , Gommans Frank , Bloem Bastiaan R. , Dirkx Michiel F. , Helmich Rick C.
Published: August 2024

Objective

Parkinson’s disease (PD) resting tremor is thought to be initiated in the basal ganglia and amplified in the cerebello-thalamo-cortical circuit. Since stress worsens tremor, the noradrenergic system may play a role in amplifying tremor. We tested if and how propranolol, a non-selective beta-adrenergic receptor antagonist, reduces PD tremor, and whether or not this effect is specific to stressful conditions.

Methods

In a cross-over, double-blind intervention study, participants with PD resting tremor received propranolol (40mg, single dose) or placebo (counter-balanced) on two different days. During both days, we assessed tremor severity (with accelerometry) and tremor-related brain activity (with functional Magnetic Resonance Imaging; fMRI), as well as heart rate and pupil diameter, while subjects performed a stressful cognitive load task that has been linked to the noradrenergic system. We tested for effects of drug (propranolol vs. placebo) and stress (cognitive load vs. rest) on tremor power and tremor-related brain activity.

Results

We included 27 PD patients with clear resting tremor. Tremor power significantly increased during cognitive load vs. rest (F(1,19)=13.8;p=.001; ηp2=0.42) and decreased by propranolol vs. placebo (F(1,19)=6.4;p=.02; ηp2=0.25), but there was no interaction. We observed task-related brain activity in a stress-sensitive cognitive control network, and tremor power-related activity in the cerebello-thalamo-cortical circuit. Propranolol significantly reduced tremor-related activity in the motor cortex compared to placebo (F(1,21)=5.3;p=.03; ηp2=0.20), irrespective of cognitive load.

Interpretation

Our findings indicate that the noradrenergic system has a general, context-independent role in amplifying PD tremor at the level of the primary motor cortex.
Distinct characteristics of lymphoid and myeloid clonal hematopoiesis in Word Trade Center first responders
Authors: Esai Selvan Myvizhi , Kuan Pei-Fen , Yang Xiaohua , Mascarenhas John , Klein Robert J. , Luft Benjamin J. , Boffetta Paolo , Gümüş Zeynep H.
Published: August 2024

BACKGROUND

Clonal hematopoiesis of indeterminate potential (CHIP) is a condition when healthy individuals harbor clonal mutations in myeloid (M-CHIP) and/or lymphoid (L-CHIP) cells at variant allele fraction (VAF) ≥0.02. While CHIP is associated with an increased risk of hematologic malignancy and cardiovascular disease, its association with airborne carcinogens is largely unknown.

OBJECTIVES

Here, we studied M/L-CHIP in responders to the 9/11 terrorist attacks on the World Trade Center (WTC), who were exposed to a complex mix of airborne carcinogens. Then we explored the association of CHIP mutations with phenotypes such as age, ancestry, exposure, HLA zygosity, and other clinical, laboratory, mental and cognitive data. Finally, we compared CHIP prevalence in WTC responders to 293 unexposed controls.

METHODS

Using banked peripheral blood and ultra-deep whole-exome sequencing at 250X, we characterized CHIP mutations and their interaction with clinical, mental and cognitive characteristics, exposure, peripheral blood counts, and HLA zygosity in 350 WTC responders. We used Fisher’s exact test for categorical variables; Wilcoxon rank sum test for continuous variables; and logistic regression for multivariate analysis.

RESULTS

Among WTC participants, M-CHIP prevalence was 16.2% and L-CHIP 21.4%. M-CHIP prevalence increased with age (p=0.02), was elevated in previous-smokers (p=0.01), and associated with lower platelet counts (p=0.03). The most frequently occurring genes for M-CHIP wereDNMT3A,TET2,PPM1Dand for L-CHIP wereEEF1A1,DDX11andKMT2D. Notably, harboring aDDX11mutation associated with a lower Montreal Cognitive Assessment score (p=6.57e-03). Overall, M/L-CHIP was more prevalent in WTC responders versus controls.

DISCUSSION

Study results will inform the development of personalized risk-adapted CHIP and cancer screening programs in individuals exposed to airborne carcinogens.
MinD2 modulates cell shape and motility in the archaeonHaloferax volcanii
Authors: Patro Megha , Sivabalasarma Shamphavi , Gfrerer Sabrina , Rodriguez-Franco Marta , Nußbaum Phillip , Ithurbide Solenne , Albers Sonja-Verena
Published: August 2024

In bacteria and archaea, proteins of the ParA/MinD family of ATPases regulate the spatiotemporal organization of various cellular cargoes, including cell division proteins, motility structures, chemotaxis systems, and chromosomes. In bacteria, such asEscherichia coli, MinD proteins are crucial for the correct placement of the Z-ring at mid-cell during cell division. However, previous studies have shown that none of the 4 MinD homologs present in the archaeonHaloferax volcaniihave a role in cell division, suggesting that these proteins regulate different cellular processes in haloarchaea. Here, we show that while deletion of MinD2 inH. volcanii(ΔminD2) does not affect cell growth or division, it impacts cell shape and motility by mispositioning the chemotaxis arrays and archaellum motors. Finally, we explore the links between MinD2 and MinD4, which has been previously shown to modulate the localization of chemosensory arrays and archaella inH. volcanii, finding that the two MinD homologues have synergistic effects in regulating the positioning of the motility machinery. Collectively, our findings identify MinD2 as an important link between cell shape and motility inH. volcaniiand further our understanding of the mechanisms by which multiple MinD proteins regulate cellular functions in haloarchaea.
Inhibition of protein or glutamine biosynthesis affect the activation of the light stimulated SBiP1 chaperone by dephosphorylation in Symbiodiniaceae
Authors: Castillo-Medina Raúl Eduardo , Islas-Flores Tania , Morales-Ruiz Estefanía , Villanueva Marco A.
Published: August 2024

Phosphorylation/dephosphorylation is fundamental for transduction of external stimuli into physiological responses. In photosynthetic dinoflagellatesSymbiodinium microadriaticumCassKB8, Thr-phosphorylated SBiP1 under dark conditions, is activated through dephosphorylation upon light stimuli. We evaluated the effect of protein synthesis inhibitors on light modulated Thr phosphorylation of SBiP1. Inhibition of cytoplasmic protein synthesis by cycloheximide but not of chloroplastic protein synthesis by chloramphenicol, promoted inactivation via Thr re-phosphorylation of the protein under the light. Additionally, inhibition of glutamine synthetase by glufosinate produced a delay in the light induced activation by dephosphorylation of the chaperone. Heat shock reverted the effect in cycloheximide-treated cells suggesting that heat stress overrides the cycloheximide-induced inactivation to restore chaperone activity. These results suggest that light and stress are critical switches of SBiP1 chaperone activity that function along with common pathways of protein synthesis and ammonia assimilation, and further confirm that the light induced SBiP1 Thr dephosphorylation is independent of photosynthesis.
Spin-orbit coupling effects in single-layer phosphorene
Authors: Peralta Mayra , Freire Dennis A. , González-Hernández Rafael , Mireles Francisco
Published: August 2024

The electronic band structure of monolayer phosphorene is thoroughly studied by considering the presence of spin-orbit interaction. We employ a multiorbital Slater-Koster tight-binding approach to derive effective k·p-type Hamiltonians that describes the dominant spin-orbit coupling (SOC) effects of the Rashba and intrinsic origin at the high Γ and S high symmetry points in phosphorene. In the absence of SOC effects a minimal admixture of pz and py atomic orbitals suffices to reproduce the well-known anisotropy of highest valence and the lowest conduction bands at the Γ point, consistent with density functional theory (DFT) and k·p methods. In contrast, the inclusion of the px and

s

atomic orbitals are rather crucial for an adequate description of the SOC effects in phosphorene at low energies, particularly at the S point. We introduce useful analytical expressions for the Rashba and intrinsic SOC parameters in terms of the relevant Slater-Koster integrals. In addition, we report simple formulas for the interband dipole strengths, revealing the nature of the strong anisotropic behavior of its lower bands. Our findings can be useful for further studies of electronic and spin transport properties in monolayer phosphorene and its nanoribbons.

Published by the American Physical Society
2024