bluuebunny/crossref_metadata_2025 huggingface dataset:
Back to the future: the persistent problems of hybrid war
Authors: Person Robert , Kulalic Isak , Mayle John
Published: June 2024

What has happened to the spectre of Russian hybrid warfare that once haunted strategists, policy-makers and scholars? Many of the characteristics of Russia's 2014 invasion of Crimea have been absent in Moscow's current war, prompting some to wonder whether Russia has moved beyond ‘hybrid warfare’ as it wages a brutal conventional war in Ukraine. Scholars and practitioners should not pack up their hybrid war handbooks just yet, however. The need to limit conflict escalation between nuclear-armed adversaries suggests that non-military asymmetric tools of will increasingly define great power competition in the twenty-first century. Most urgently, scholars must bring some order to the conceptual debate over what is and is not hybrid war. In this policy paper, we propose a classification scheme that can be applied irrespective of the type of conflict, one that illuminates the wide range of political, social, economic and military weapons states may use in future conflicts. This approach not only allows us to move beyond endless debates over which tactics belong in the definition of hybrid war, but it also allows us to describe changes over time in how countries wage multi-domain wars. By describing the ‘hybridity’ of all conflict along three continuous axes of scale, militarization and centralization, scholars and policy-makers alike can avoid dangerous blind spots that are likely to arise when we try to categorize conflicts into discrete typological bins.
Are Video Games and School Conflictual or Complementary Contexts for Affording Psychological Need Fulfillment? Implications for Adolescents’ Problematic Gaming and School Adjustment
Authors: Bradt Lowie , Vermote Branko , Zaman Bieke , Vansteenkiste Maarten , Van de Casteele Marlies , Soenens Bart
Published: June 2024

According to the need density hypothesis, adolescents are at risk for problematic gaming when they only experience satisfaction of their basic psychological needs within, but not outside, the gaming context. This cross-sectional study among daily gamers (N = 309, M age = 15.63, 94.8% boys) is the first to examine this hypothesis in adolescence, thereby comparing adolescents’ need fulfillment between the contexts of video games and school and examining the role of need fulfilment in both contexts in relation to problematic gaming and school outcomes. Response surface analysis showed that adolescents’ overall need satisfaction (across the two contexts) was related to lower problematic gaming and less maladaptive school outcomes. Consistent with the need density hypothesis, adolescents reported more problematic gaming, school disengagement and school burnout when high need satisfaction in the gaming context co-occurred with either low need satisfaction or high need frustration at school. Directions for future research are discussed.
The d-elements of precoherent preidempotent quantales and their applications
Authors: Ruan Xianglong
Published: June 2024

In this paper, we introduce the notion of d-elements on precoherent preidempotent quantale (PIQ), construct Zariski topology on $Max(Q_{d})$ and explore its various properties. Firstly, we give a sufficient condition of a topological space $Max(Q_{d})$ being Hausdorff. Secondly, we prove that if $ P=\mathfrak{B}(P) $ and $ Q=\mathfrak{B}(Q) $, then $P$ is isomorphic to $Q$ iff $ Max(P_{d}) $ is homeomorphic to $ Max(Q_{d}) $. Moreover, we prove that $ (P\otimes Q)_{d} $ is isomorphic to $ P_{d} \otimes Q_{d} $ iff $ P_{d} \otimes Q_{d}=(P_{d} \otimes Q_{d})_{d} $. Finally, we prove that the category $ \textbf{dPFrm} $ is a reflective subcategory of $\textbf{PIQuant}.$
The tumor suppressor Fat1 is dispensable for normal murine hematopoiesis
Authors: Zhang Qing , Li Meng Ke , Hu Xin Yuan , Wu Yu Xin , Wang Ying Ying , Zhao Pan Pan , Cheng Lin Na , Yu Rong Hua , Zhang Xu Dong , Chen Song , Zhu Zun Min , de Bock Charles E , Thorne Rick F
Published: June 2024

Loss and overexpression of FAT1 occurs among different cancers, with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets (i.e. sustained following transformation), predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout mice in which Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multipanel flow cytometry revealed no ostensible differences between Fat1 conditional knockout mice and normal littermates. Further functional comparisons involving colony-forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.
Comparative susceptibility of adult house fly (Diptera: Muscidae) and an important predator, Carcinops pumilio (Coleoptera: Histeridae), to Beauveria bassiana (Hypocreales: Cordycipitaceae)
Authors: Geden Christopher J , White Roxie L , Pagac Alexandra A , Machtinger Erika T
Published: June 2024

House flies (Musca domestica L.) (Diptera: Muscidae) are challenging pests to control. Biological control using Carcinops pumilio beetles may help to reduce house fly populations. However, it is unknown if C. pumilio beetles are compatible with Beauveria bassiana, another house fly biological control option. Five strains of commercially available (GHA, HF23, and L90) and newly discovered (NFH10 and PSU1) strains of B. bassiana were used to test the comparative susceptibility of adult house flies and adult C. pumilio using different laboratory exposure methods. Adult house flies were susceptible to B. bassiana in contact filter paper assays (89%–98% mortality) and immersion assays (100% mortality) at the same 108 conidia suspension using 0.1% CapSil as an aqueous surfactant. Carcinops pumilio were less susceptible than flies to B. bassiana infection using the contact and immersion assays at the same 108 conidial concentration, with 4.4%–12.2% and 8.3%–24.6% mortality, respectively. Immersion in an aqueous conidial suspension resulted in higher mortality compared to contact with treated filter papers at the same 108 concentration with house flies and beetles. We conclude that C. pumilio can safely be used as a biological control agent for house flies with B. bassiana in animal production systems.
Significant strides: Women’s advancement in endurance sports
Authors: McKay Bowen Claire
Published: June 2024

In a break with tradition, the culminating event of the Paris 2024 Olympic Games will be the women’s marathon, not the men’s. Women have come a long way over the last century in being able to participate – and smash records – in endurance sports such as marathons, ultra-marathons, long-distance cycling and swimming, and triathlons. Claire McKay Bowen explores what has helped, and hindered, them along the way
Simultaneous repair of diaphragmatic hernia and ventricular septal defect with postoperative complication in a Down syndrome child
Authors: Almutairi Marshad A , Sultan Abdulsamad F , Alariefy Abdulaziz A , Alzahrani Nada A , Baghaffar Abdullah H , Al-Radi Osman O
Published: June 2024

Morgagni hernia (MH) is a rare form of congenital diaphragmatic hernia, typically occurring predominantly on the right side and exhibiting a higher prevalence in females. Usually diagnosed incidentally, MH may coexist with congenital heart defects, chest wall abnormalities and certain genetic syndromes such as Down syndrome. A 4-year-old boy with Down syndrome underwent simultaneous repair of MH and closure of a ventricular septal defect (VSD). A vertical midline sternotomy was performed, and the VSD was repaired using the right atrium approach. Subsequently, MH repair was conducted. Three weeks after the surgery, this patient developed a complete heart block, which lead to the implantation of a VVI pacemaker.
The Impact of Exposure to Food and Drug Administration E-cigarette Authorization Messages on Product Perceptions and Interest—An Experiment With Adults Who Smoke and Youth
Authors: Wackowski Olivia A , Jeong Michelle , Gratale Stefanie K , Weiger Caitlin , Chen-Sankey Julia , Strasser Andrew A , Delnevo Cristine D
Published: June 2024

Introduction

In the United States, e-cigarettes have entered a new regulatory era, needing authorizations from the Food and Drug Administration (FDA) to remain on or enter the marketplace. This study explored the impact of e-cigarette authorization messages on product perceptions and interests.

Aims and Methods

We conducted an online experiment in June 2022 with nationally representative samples of adults (≥21) who smoke cigarettes (n = 866) and youth ages 15–20 (n = 859). They were randomized to one of five conditions: Viewing an ad for a fictional e-cigarette brand with no reference to the FDA (control), an ad with an “authorized for sale by FDA” claim in varying presentation styles (plain text, FDA “approved” stamp, FDA logo), or reading a fictional news excerpt about the product’s authorization plus control ad. We compared group differences in product interest, susceptibility, harm perceptions, and message perceptions.

Results

Among adults who smoke, there were no effects on product interest nor susceptibility, but ratings of the product’s harmfulness compared to cigarettes were lower among those in the news versus control condition (β = −0.25, p = .04). Among youth, odds of susceptibility were higher among ever e-cigarette users who viewed the ad with the FDA logo authorization message relative to the control ad (OR = 6.3, 95% CI:1.67 to 23.9, p < .01). About 40% of all participants agreed the authorization claim makes them think the product is safe to use, but fewer (14%–19%) agreed it makes them more interested in trying it.

Conclusions

FDA e-cigarette authorization messages may impact some product harm beliefs. More research is needed to track potential impacts on product use and on ways to promote accurate message understanding.

Implications

This study provides new data about the potential impact of messages about FDA authorization of e-cigarette products (presented as ad claims or a news story) on authorized product perceptions, interest, and susceptibility among adults who smoke cigarettes and youth. Our results suggest that FDA e-cigarette authorization messages may impact harm-related beliefs among adults who smoke and product susceptibility among youth who have ever used e-cigarettes before, though real-world effects are likely to be impacted by message type and format, and perceived message source and credibility. Authorization messages are likely to be misinterpreted as “FDA approval” by some; therefore, providing clarifications about authorization meaning and standards are relevant where possible.
The Frontiers of Nullification and Anticommandeering: Federalism and Extrajudicial Constitutional Interpretation
Authors: Hartery Jesse , Sigalet Geoffrey T
Published: June 2024

In federal systems, non-judicial actors can engage in constitutional reasoning. The actions taken may come in different legal forms. Some may be consistent with positive law, while others may not. Nullification and anticommandeering are prominent examples. We show that these concepts have functionally made new appearances in Canada. One significant example of this is Alberta’s enactment of the 2022 Sovereignty Act. We trace how the initial proposal for the legislation resembled nullification. Over time, the proposal was reformed to adapt it to the particularities of Canadian federalism. The result was a Sovereignty Act that appears to assert existing provincial powers, particularly as a formal framework for extrajudicial constitutional interpretation via anticommandeering, although only time will tell if this remains the case in practice. In doing so, we shine a light on the contours of some of the legal and political debates that may arise as the framework is operationalized.
Association of Problematic Internet Use With Psychotic Experiences and Depression in Adolescents: A Cohort Study
Authors: Narita Zui , Ando Shuntaro , Yamasaki Syudo , Miyashita Mitsuhiro , DeVylder Jordan , Yamaguchi Satoshi , Hosozawa Mariko , Nakanishi Miharu , Hiraiwa-Hasegawa Mariko , Furukawa Toshiaki A , Kasai Kiyoto , Nishida Atsushi
Published: June 2024

Background and Hypothesis

Problematic internet use (PIU) is prevalent among adolescents. Past research suggested cross-sectional associations between PIU and psychotic experiences, but little information is available on the longitudinal association. We hypothesized that PIU in adolescence may be longitudinally associated with psychotic experiences, adjusting for confounders.

Study Design

We analyzed a random sample of adolescents in the Tokyo Teen Cohort to examine how PIU at ages 10 (2012–2015), 12 (2014–2017), and 16 (2019–2021) was associated with mental health issues at age 16. PIU was evaluated by the modified Compulsive Internet Use Scale, psychotic experiences by the Adolescent Psychotic-like Symptom Screener, and depression by the Short Mood and Feelings Questionnaire. We also examined the mediating role of social withdrawal.

Study Results

We analyzed 3171 adolescents; 151 reported psychotic experiences and 327 reported depression at age 16. Compared with the lowest tertile PIU group, the highest tertile PIU group at age 12 showed an increased adjusted risk of psychotic experiences (RD 3.3%, 95% CI 2.9%–3.7%; RR 1.65, 95% CI 1.55–1.73) and depression (RD 5.9%, 95% CI 5.5%–6.3%; RR 1.61, 95% CI 1.55–1.68) at age 16. PIU at age 16 showed analogous results, while PIU at age 10 suggested a smaller impact. Social withdrawal mediated 9.4%–29.0% of the association between PIU and psychotic experiences.

Conclusions

PIU is longitudinally associated with psychotic experiences and depression in adolescents. Further longitudinal and intervention studies are warranted to provide robust public health implications and foster a safer digital future.
Dysregulated Transcript Expression but Not Function of the Glutamate Transporter EAAT2 in the Dorsolateral Prefrontal Cortex in Schizophrenia
Authors: O’Donovan Sinead M , Shan Dan , Wu Xiaojun , Choi Jae Hyuk , McCullumsmith Robert E
Published: June 2024

Background

Schizophrenia (SCZ) is a serious mental illness with complex pathology, including abnormalities in the glutamate system. Glutamate is rapidly removed from the synapse by excitatory amino acid transporters (EAATs). Changes in the expression and localization of the primary glutamate transporter EAAT2 are found in the brain in central nervous system (CNS) disorders including SCZ. We hypothesize that neuronal expression and function of EAAT2 are increased in the frontal cortex in subjects diagnosed with SCZ.

Study Design

EAAT2 protein expression and glutamate transporter function were assayed in synaptosome preparations from the dorsolateral prefrontal cortex (DLPFC) of SCZ subjects and age- and sex-matched nonpsychiatrically ill controls. EAAT2 splice variant transcript expression was assayed in enriched populations of neurons and astrocytes from the DLPFC. Pathway analysis of publicly available transcriptomic datasets was carried out to identify biological changes associated with EAAT2 perturbation in different cell types.

Results

We found no significant changes in EAAT2 protein expression or glutamate uptake in the DLPFC in SCZ subjects compared with controls (n = 10/group). Transcript expression of EAAT2 and signaling molecules associated with EAAT2b trafficking (CaMKIIa and DLG1) were significantly altered in enriched populations of astrocytes and pyramidal neurons (P < .05) in SCZ (n = 16/group). These changes were not associated with antipsychotic medications. Pathway analysis also identified cell-type-specific enrichment of biological pathways associated with perturbation of astrocyte (immune pathways) and neuronal (metabolic pathways) EAAT2 expression.

Conclusions

Overall, these data support the growing body of evidence for the role of dysregulation of the glutamate system in the pathophysiology of SCZ.
Unlocking cellular plasticity: enhancing human iPSC reprogramming through bromodomain inhibition and extracellular matrix gene expression regulation
Authors: Yang Jun , Kinyamu H Karimi , Ward James M , Scappini Erica , Muse Ginger , Archer Trevor K
Published: June 2024

The transformation from a fibroblast mesenchymal cell state to an epithelial-like state is critical for induced pluripotent stem cell (iPSC) reprogramming. In this report, we describe studies with PFI-3, a small-molecule inhibitor that specifically targets the bromodomains of SMARCA2/4 and PBRM1 subunits of SWI/SNF complex, as an enhancer of iPSC reprogramming efficiency. Our findings reveal that PFI-3 induces cellular plasticity in multiple human dermal fibroblasts, leading to a mesenchymal-epithelial transition during iPSC formation. This transition is characterized by the upregulation of E-cadherin expression, a key protein involved in epithelial cell adhesion. Additionally, we identified COL11A1 as a reprogramming barrier and demonstrated COL11A1 knockdown increased reprogramming efficiency. Notably, we found that PFI-3 significantly reduced the expression of numerous extracellular matrix (ECM) genes, particularly those involved in collagen assembly. Our research provides key insights into the early stages of iPSC reprogramming, highlighting the crucial role of ECM changes and cellular plasticity in this process.
Perfluorooctanoic acid triggers premature ovarian insufficiency by impairing NAD+ synthesis and mitochondrial function in adult zebrafish
Authors: Xu Hao , Mao Xiaoyu , Zhang Siling , Ren Jie , Jiang Shanwen , Cai Lijuan , Miao Xiaomin , Tao Yixi , Peng Chao , Lv Mengzhu , Li Yun
Published: June 2024

High-dose perfluorooctanoic acid (PFOA) impairs oocyte maturation and offspring quality. However, the physiological concentrations of PFOA in follicular fluids of patients with premature ovarian insufficiency (POI) were detected at lower levels, thus the relationship between physiological PFOA and reproductive disorders remains elusive. Here, we investigated whether physiological PFOA exposure affects gonad function in adult zebrafish. Physiological PFOA exposure resulted in POI-like phenotypes in adult females, which exhibited decreased spawning frequency, reduced number of ovulated eggs, abnormal gonadal index, and aberrant embryonic mortality. Meanwhile, oocytes from PFOA-exposed zebrafish showed mitochondrial disintegration and diminished mitochondrial membrane potential. Unlike the high-dose treated oocytes exhibiting high reactive oxygen species (ROS) levels and excessive apoptosis, physiological PFOA reduced the ROS levels and did not trigger apoptosis. Interestingly, physiological PFOA exposure would not affect testis function, indicating specific toxicity in females. Mechanistically, PFOA suppressed the NAD+ biosynthesis and impaired mitochondrial function in oocytes, thus disrupting oocyte maturation and ovarian fertility. Nicotinamide mononucleotide (NMN), a precursor for NAD+ biosynthesis, alleviated the PFOA-induced toxic effects in oocytes and improved the oocyte maturation and fertility upon PFOA exposure. Our findings discover new insights into PFOA-induced reproductive toxicity and provide NMN as a potential drug for POI therapy.
Sleep as an Important Target or Modifier in Alcohol Use Disorder Clinical Treatment: Example From a Recent Gabapentin Randomized Clinical Trial
Authors: Hoffman Michaela , Voronin Konstantin , Book Sarah W. , Prisciandaro James , Bristol Emily J. , Anton Raymond F.
Published: June 2024

Objectives

Alcohol consumption affects sleep both in healthy populations and in patients with alcohol use disorder (AUD). However, sleep has typically not been considered within AUD pharmacotherapy trials. We used data from a completed gabapentin clinical treatment trial to explore the medication’s effect on patient-rated insomnia measured by a standard insomnia rating (Insomnia Severity Index [ISI]) and whether this influenced gabapentin’s effects on alcohol consumption.

Methods

This study included 90 individuals with current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition AUD criteria reporting current or past alcohol withdrawal. Participants were assigned to placebo or gabapentin (up to 1200 mg/day) for a 16-week randomized controlled trial with percent heavy drinking days (PHDD) and percent abstinent days (PDA) as outcomes. Utilizing mixed-effects models, this study assessed medication effects on ISI over the trial. We then examined the interaction of baseline ISI and medication on drinking. Finally, given our previous finding of alcohol withdrawal influencing gabapentin efficacy, we added change in ISI as a potential “moderator” of the interaction of medication effects and alcohol withdrawal on drinking.

Results

Sleep (ISI) improved more in those treated with gabapentin (60.6% reduction) compared with placebo (37.8% reduction; P = 0.013). Higher baseline ISI predicted drinking in gabapentin-treated individuals (lower PHDD [P = 0.026] and higher (PDA [P = 0.047]). ISI was an independent predictor of PHDD decrease and PDA increase (P < 0.001; P = 0.002), but this did not significantly moderate gabapentin’s effectiveness.

Conclusions

Although gabapentin positively impacts both alcohol use and sleep, its effect on drinking is not fully dependent on sleep improvement, implying a direct biological mechanism on alcohol use.
Neoadjuvant and adjuvant systemic therapy in HCC: Current status and the future
Authors: Singal Amit G. , Yarchoan Mark , Yopp Adam , Sapisochin Gonzalo , Pinato David J. , Pillai Anjana
Published: June 2024

Surgical therapies in patients with early-stage HCC can afford long-term survival but are often limited by the continued risk of recurrence, underscoring an interest in (neo)adjuvant strategies. Prior attempts at adjuvant therapy using tyrosine kinase inhibitors failed to yield significant improvements in recurrence-free survival or overall survival. Advances in the efficacy of systemic therapy options, including the introduction of immune checkpoint inhibitors, have fueled renewed interest in this area. Indeed, the IMBrave050 trial recently demonstrated significant improvements in recurrence-free survival with 1 year of adjuvant atezolizumab plus bevacizumab in high-risk patients undergoing surgical resection or ablation, with several other ongoing trials in this space. There is a strong rationale for consideration of the administration of these therapies in the neoadjuvant setting, supported by early clinical data demonstrating high rates of objective responses, although larger trials examining downstream outcomes are necessary, particularly considering the possible risks of this strategy. In parallel, there has been increased interest in using systemic therapies as a bridging or downstaging strategy for liver transplantation. Current data suggest the short-term safety of this approach, with acceptable rates of rejection, so immunotherapy is not considered a contraindication to transplant; however, larger studies are needed to evaluate the incremental value of this approach over locoregional therapy. Conversely, the use of immunotherapy is currently discouraged after liver transplantation, given the high risk of graft rejection and death. The increasing complexity of HCC management and increased consideration of (neo)adjuvant strategies highlight the critical role of multidisciplinary care when making these decisions.
Proteomic analysis of serum extracellular vesicles reveals Fibulin-3 as a new marker predicting liver-related events in MASLD
Authors: Sakane Sadatsugu , Hikita Hayato , Shirai Kumiko , Sakamoto Tatsuya , Narumi Ryohei , Adachi Jun , Kakita Naruyasu , Yamada Yukinori , Toyoda Hidenori , Takahashi Hirokazu , Suda Goki , Kai Machiko , Tahata Yuki , Sakamori Ryotaro , Kumazaki Shusuke , Fukumoto Kenji , Myojin Yuta , Murai Kazuhiro , Kodama Takahiro , Tatsumi Tomohide , Tomonaga Takeshi , Sakamoto Naoya , Morii Eiichi , Takehara Tetsuo
Published: June 2024

Background:

There is a need for novel noninvasive markers for metabolic dysfunction–associated steatotic liver disease (MASLD) to stratify patients at high risk for liver-related events including liver cancer and decompensation. In the present study, we used proteomic analysis of proteins in extracellular vesicles (EVs) to identify new biomarkers that change with fibrosis progression and can predict the development of liver-related events.

Methods:

We analyzed serum EVs from 50 patients with MASLD assessed for liver fibrosis by biopsy and identified proteins that altered with advanced fibrosis. A further evaluation was conducted on another cohort of 463 patients with MASLD with biopsy.

Results:

Eight candidate proteins were identified by proteomic analysis of serum EVs. Among them, serum levels of Fibulin-3, Fibulin-1, and Ficolin 1 correlated with their EV levels. In addition, serum Fibulin-3 and serum Fibulin-1 levels changed significantly with advanced fibrosis. Using another cohort with biopsy, we found that the serum Fibulin-3 concentration was significantly greater in those with advanced fibrosis but that the serum Fibulin-1 concentration was not significantly different. Multivariate Cox proportional hazards analysis revealed that a higher Fibrosis-4 (FIB-4) index and higher serum Fibulin-3 concentration were independent risk factors for liver-related events. When the cutoff value for the serum Fibulin-3 concentration was 6.0 µg/mL according to the Youden index of AUROCs, patients with high serum Fibulin-3 significantly more frequently developed liver-related events than did other patients. Validation using another cohort of 226 patients with clinically diagnosed MASLD confirmed that high serum Fibulin-3 levels are associated with a greater frequency of liver-related events.

Conclusions:

Serum Fibulin-3 was identified as a biomarker for predicting liver-related events in patients with MASLD.
Principal Component Analysis of a Real-World Cohort of Descemet Stripping Automated Endothelial Keratoplasty and Descemet Membrane Endothelial Keratoplasty Cases: Demonstration of a Powerful Data-Mining Technique for Identifying Areas of Research
Authors: Perone Jean-Marc , Goetz Christophe , Zevering Yinka , Derumigny Alexis
Published: June 2024

Purpose:

Principal component analysis (PCA) is a descriptive exploratory statistical technique that is widely used in complex fields for data mining. However, it is rarely used in ophthalmology. We explored its research potential with a large series of eyes that underwent 3 keratoplasty techniques: Descemet membrane endothelial keratoplasty (DMEK), conventional Descemet stripping automated endothelial keratoplasty (ConDSAEK), or ultrathin-DSAEK (UT-DSAEK).

Methods:

All consecutive DMEK/DSAEK cases conducted in 2016 to 2022 that had ≥24 months of follow-up were included. ConDSAEK and UT-DSAEK were defined as preoperative central graft thickness ≥130 and <130 μm, respectively. Seventy-six patient, disease, surgical practice, and temporal outcome variables were subjected to PCA, including preoperative anterior keratometry, the use of sulfur hexafluoride gas (SF6) versus air for primary tamponade, and postoperative best corrected visual acuity and endothelial cell density. Associations of interest that were revealed by PCA were assessed with the Welch t test or Pearson test.

Results:

A total of 331 eyes were treated with DMEK (n = 165), ConDSAEK (n = 95), or UT-DSAEK (n = 71). PCA showed that ConDSAEK and UT-DSAEK clustered closely, including regarding postoperative best corrected visual acuity, and were clearly distinct from DMEK. PCA and follow-up univariate analyses suggested that in DMEK, 1) flatter preoperative anterior keratometry (average, K1, and K2) associated with more rebubbling (P = 0.004–0.089) and graft detachment (P = 0.007–0.022); 2) graft marking did not affect postoperative endothelial cell density; and 3) lower postoperative endothelial cell density associated with SF6 use (all P > 0.001) and longer surgery (P = 0.005–0.091). All associations are currently under additional investigation in our hospital.

Conclusions:

PCA is a powerful technique that can rapidly reveal clinically relevant associations in complex ophthalmological datasets.
Learning pathways composed of core subjects with features of reducing cognitive load have better learning outcomes
Authors: Huang Shiau-Shian , Huang Anna YuQing , Lin Yu-Fan , Lin Sheng-Min , Webster Craig S. , Lin Ji-Yang , Yang Ying-Ying , Yang Stephen J.H. , Lirng Jiing-Feng , Chen Chen-Huan , Yang Albert ChihChieh , Lin Chi-Hung
Published: June 2024

Background:

Changing the course duration or timing of subjects in learning pathways would influence medical students’ learning outcomes. Curriculum designers need to consider the strategy of reducing cognitive load and evaluate it continuously. Our institution underwent gradual curricular changes characterized by reducing cognitive load since 2000. Therefore, we wanted to explore the impact of this strategy on our previous cohorts.

Methods:

This cohort study explored learning pathways across academic years of more than a decade since 2000. Eight hundred eighty-two medical students between 2006 and 2012 were included eventually. Learning outcomes included an average and individual scores of subjects in different stages. Core subjects were identified as those where changes in duration or timing would influence learning outcomes and constitute different learning pathways. We examined whether the promising learning pathway defined as the pathway with the most features of reducing cognitive load has higher learning outcomes than other learning pathways in the exploring dataset. The relationship between features and learning outcomes was validated by learning pathways selected in the remaining dataset.

Results:

We found nine core subjects, constituting four different learning pathways. Two features of extended course duration and increased proximity between core subjects of basic science and clinical medicine were identified in the promising learning pathway 2012, which also had the highest learning outcomes. Other pathways had some of the features, and pathway 2006 without such features had the lowest learning outcomes. The relationship between higher learning outcomes and cognitive load-reducing features was validated by comparing learning outcomes in two pathways with and without similar features of the promising learning pathway.

Conclusion:

An approach to finding a promising learning pathway facilitating students’ learning outcomes was validated. Curricular designers may implement similar design to explore the promising learning pathway while considering potential confounding factors, including students, medical educators, and learning design of the course.
Phase angle is an indicator of GLIM-diagnosed malnutrition in patients undergoing major pancreatic and biliary surgery: a cross-sectional study
Authors: Wang Lijuan , Li Pengxue , Hu Yifu , Cheng Bo , Li Lei , Ding Lili , Song Jinghai , Wei Junmin , Xu Jingyong
Published: June 2024

Objective:

The aim of this study is to elucidate the correlation between phase angle and malnutrition, and to determine the malnutrition cut-off points based on phase angle in patients undergoing major pancreatic and biliary surgery.

Methods:

This is a cross-sectional study analyzing the prospective database of the Department of Hepatopancreatobiliary Surgery at Beijing Hospital, China, from December 2020 to September 2023. Basal data, diet surveys, anthropometry, and body composition were recorded. Phase angle was measured with the InBody 720. The GLIM criteria were used to diagnose malnutrition. Subgroup analyses were conducted by stratifying age and pancreatic cancer.

Results:

A total of 185 consecutive cases were included, with a mean age of 63.66;±11.96 years. 63.8% (118/185) of the participants were aged 60 years or older, and 43.8% (81/185) were diagnosed with pancreatic cancer. The prevalence of malnutrition was 62.2% among all subjects, 67.8% among the elderly, and 69.1% among pancreatic cancer patients. Phase angle was significantly lower in the malnourished group than in the normal group. Positive correlations were found between phase angle and BMI, ASMI, FFMI, fat-free mass, total energy intake, grip strength, calf circumference, 6-meter timed walk speed, total protein, albumin, and prealbumin. Among all the subjects, participants with a lower phase angle were significantly more likely to suffer from malnutrition than their control group, with a 1.611 times higher risk (95% CI 1.013-2.562, P=0.044). The cut-off points of the phase angle for determining malnutrition were 4.82 in men (sensitivity 0.744, specificity 0.571, area under the curve 0.667, 95% CI 0.567-0.766, P = 0.003), and 4.54 in women (sensitivity 0.750, specificity 0.711, area under the curve 0.757, 95% CI 0.644-0.869, P < 0.001). In the subgroup analyses of elderly and pancreatic cancer patients, we obtained consistent results with statistical significance and identified corresponding cut-off points.

Conclusion:

The present study suggests that the phase angle could be a valid, useful, and simple indicator of malnutrition in patients undergoing major pancreatic and biliary surgery.
N-terminal pro–B-type natriuretic peptide and pulmonary echography are predictors of acute heart failure needing early mechanical ventilation in acute coronary syndrome
Authors: Cristo-Ropero María J. , Garcia-Rubira Juan C. , Rivera-Rabanal Francisco Javier , Seoane-García Tania , Madrona-Jiménez Luis , Izquierdo-Bajo Álvaro , Hernández-Meneses Begoña , Vilches-Arenas Angel , Hidalgo-Urbano Rafael
Published: June 2024

Aim

The aim of this study was to determine the best clinical predictors of acute heart failure needing mechanical ventilation (MV) in the first 48 h of evolution of patients admitted because of acute coronary syndrome (ACS).

Methods

We analyzed a cohort of patients admitted for ACS between February 2017 and February 2018. A pulmonary ultrasound was performed on admission and was considered positive (PE+) when there were three or more B-lines in two quadrants or more of each hemithorax. It was compared with N-terminal pro–B-type natriuretic peptide (NT-proBNP), peak troponin T-us value GRACE (Global Registry of Acute Coronary Events), CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology and American Heart Association guidelines – Bleeding Score), CACS (Canada Acute Coronary Syndrome risk score), and HAMIOT (Heart Failure after Acute Myocardial Infarction with Optimal Treatment score) scores, shock index, ejection fraction, chest X-ray, and Killip class at admission as predictors of MV in the first 48 h of admission.

Results

A total of 119 patients were included: 54.6% with ST elevation and 45.4% without ST elevation. Twelve patients (10.1%) required MV in the first 48 h of evolution. The sensitivity of PE+ was 100% (73.5–100%), specificity 91.6% (84.6–96.1%), and area under the curve was 0.96 (0.93–0.96). The sensitivity of an NT-proBNP value more than 3647 was 88.9% (51.9–99.7%), specificity 92.1% (84.5–96.8%), and area under the curve was 0.905 (0.793–1). The κ statistic between both predictors was 0.579. All the other scores were significantly worse than PE + .

Conclusion

Lung ultrasound and a high NT-proBNP (3647 ng/L in our series) on admission are the best predictors of acute heart failure needing MV in the first 48 h of ACS. The agreement between both tests was only moderate.
Compartment syndrome of arm secondary to snake bite on hand: a case report
Authors: Dahal Amartya , Basi Ashkal , Shrestha Rohit , Khadka Sushant K. , Das Arjun , Malla Manasil , Dahal Arshima , Chaudhary Aashutosh
Published: June 2024

Introduction:

Snake bites pose a significant common public health concern, with more prevalence in rural areas. Compartment syndrome (CS) is one of the rare and severe manifestations of snake bite wherein venom-induced swelling within a closed anatomical compartment leads to increased pressure, which may result in ischemic damage to nerves and muscle. Antisnake venom and prompt fasciotomy is recommended for management of CS secondary to snake bite.

Case details:

Here, the authors report a case of 47-year-old female with Green Pit Viper bite on the left hand. Upon arrival to hospital, initial resuscitation measures were initiated. Six hours following the bite, there was severe pain on passive stretch and paresthesia. Ten vials of antisnake venom administration along with fasciotomy of hand and arm resulted in notable alleviation of pain and swelling. Eighteen pints of blood was transfused for coagulopathy and low hemoglobin. After continued care of wound and intensive physiotherapy, functional limb could be achieved.

Discussion:

Snake bite envenomation is one of the biggest hidden health crises with case fatality rate of 7.8% in the southern plains of Nepal. As in our case, snake bites commonly affect upper extremities, accounting for around two third of all cases. CS must be differentiated from acute swelling, which sometimes may be difficult. Surgical decompression is indicated in presence of signs and symptoms of CS, in case of resource limited setting.

Conclusion:

Multidisciplinary and prompt management with initial resuscitation, ASV administration, fasciotomy, and rehabilitative measures can save both life and limb in such cases.
An exploration of clinical features and factors associated with pain frequency and pain intensity in children with growing pains: a cross-sectional study from Chongqing, China
Authors: Zhang Wenni , Xu Ximing , Leng Hongyao , Shen Qiao , Lu Qiufan , Zheng Xianlan
Published: June 2024

Instruction:

Growing pains are the most common cause of musculoskeletal pain in children, affecting both children's and caregivers' well-being. The lack of definitive diagnostic criteria complicates diagnosis and treatment.

Objectives:

This study aims to outline the clinical features and identify factors associated with the frequency and intensity of growing pains in children in Chongqing, China.

Methods:

A cross-sectional study was conducted in a children's hospital using its Internet hospital follow-up platform. Children initially diagnosed with growing pains between July and September 2022 were enrolled. Sociodemographics, pain locations, duration, frequency, intensity, and potentially related factors were collected.

Results:

Eight hundred sixty-three children were enrolled (average age: 8.19 ± 3.24 years; 455 boys [52.72%]). Pain frequency was reported as quarterly (62.11%), monthly (24.80%), biweekly (1.74%), weekly (10.08%), and daily (1.27%). The prevalence of mild, moderate, and severe pain was 26.65%, 55.74%, and 17.61%, respectively. The knee was the most common pain location (63.85%), mostly encountered between 4 pm and 5 pm (20.51%). Multivariate analysis revealed that pain frequency negatively correlated with vitamin supplementation during pregnancy, positively correlated with underweight, bad temper, increased exercise, and cold lower extremities. Pain intensity positively correlated with irritability, increased exercise, and pain sensitivity but negatively correlated with age and vitamin supplementation during lactation.

Conclusion:

Growing pains typically occur on a quarterly basis, predominantly affecting the knees during 4 pm to 5 pm. Factors in sociodemographics, maternal aspect, temperament, and exercise levels can influence pain frequency and intensity. Clinicians should consider these aspects when developing comprehensive strategies for pain management.
Freezing of gait: pharmacological and surgical options
Authors: Gámez-Leyva Gonzalo , Cubo Esther
Published: June 2024

Purpose of review

The primary aim of this review is to describe and update the pathophysiological and relevant therapeutic strategies for freezing of gait (FoG) in patients with Parkinson's disease (PD).

Recent findings

FoG presumably involves dysfunction of multiple cortical and subcortical components, including dopaminergic and nondopaminergic circuits. In this regard, levodopa and physical therapy represent the first-choice therapeutic options for PD patients with FoG. However, the relationship between FoG and levodopa is not fully predictable. For those patients with levodopa-resistant FoG, there is promising but still controversial data on the benefits of bilateral high-frequency transcranial magnetic stimulation and deep brain stimulation on the subthalamic nuclei, substantia nigra pars reticulata, pedunculopontine nucleus, and the Fields of Forel. On the other hand, general exercise, gait training with a treadmill, focus attention on gait training, and conventional physiotherapy have demonstrated moderate to large benefits in FoG.

FOG requires different treatment strategies. The inclusion of adequate detection and prediction of FoG combined with double-blind, and statistically powered protocols are needed to improve patients’ quality of life, the motor and nonmotor symptoms and societal burden associated with FoG.
Ancestral SARS-CoV-2 immune imprinting persists on RBD but not NTD after sequential Omicron infections
Authors: Wang Zuowei , Li Ling , Du Ruiping , Chen Xixian , Sun Yi , Qin Rongrong , Li Yunjian , Feng Hualong , Hu Lin , Chen Xuanyi , Lu Maosheng , Jiang Liwei , Zuo Teng
Published: June 2024

Whether Omicron exposures could overcome ancestral SARS-CoV-2 immune imprinting remains controversial. Here we analyzed B cell responses evoked by sequential Omicron infections in vaccinated and unvaccinated individuals. Plasma neutralizing antibody titers against ancestral SARS-CoV-2 and variants indicate that immune imprinting is not consistently induced by inactivated or recombinant protein vaccines. However, once induced, immune imprinting is not countered by successive Omicron challenges. We compared binding specificities, neutralizing capacities, developing origins and targeting epitopes of monoclonal antibodies from individuals with or without immune imprinting. Although receptor-binding domain (RBD) and N-terminal domain (NTD) of spike are both primary targets for neutralizing antibodies, immune imprinting only shapes antibody responses to RBD by impeding the production of Omicron-specific neutralizing antibodies while facilitating the development of broadly neutralizing antibodies. We propose that immune imprinting can be either neglected by NTD-based vaccines to induce variant-specific antibodies or leveraged by RBD-based vaccines to induce broadly neutralizing antibodies.
Tormentor: An obelisk prediction and annotation pipeline
Authors: Kremer Frederico Schmitt , de Barros Danielle Ribeiro
Published: June 2024

Obelisks are circular RNA viroid-like elements first described in January 2024 and identified through RNA-Seq data analysis. These elements are widespread in human gut samples. and characterized by their rod-like secondary structure reminiscent of obelisk monuments, exhibiting an average size of approximately 1,000 base pairs. Despite their initial identification, little is known about their biogenesis and their potential impact on human physiology and the microbiome. To facilitate further exploration in this emerging field, we developed Tormentor, an automated pipeline designed for the identification and annotation of Obelisks from stranded RNA-Seq data, leveraging methodologies similar to those employed in their initial discovery. To our knowledge, this is the first tool specialized for the identification of these elements.
ScSNViz: a user-friendly toolset for visualization and analysis of Cell-Specific Expressed SNVs
Authors: Kim Allen , Martinez Siera , Edwards Nathan , Horvath Anelia
Published: June 2024

Motivation

Understanding genetic variation at the single-cell level is crucial for insights into cellular heterogeneity, clonal evolution, and gene expression regulation, but there is a scarcity of tools for visualizing and analyzing cell-level genetic variants.

Results

We introduce scSNViz, a comprehensive R-based toolset for visualization and analysis of cell-specific expressed Single Nucleotide Variants (sceSNVs) within cell-barcoded single-cell RNA-sequencing (scRNA-seq) data. ScSNViz offers 3D sceSNV visualization capabilities for dimensionally reduced scRNA-seq gene expression data, compatibility with popular scRNA-seq processing tools like Seurat, cell-type classification tools such as SingleR and scType, and trajectory inference computation using Slingshot. Furthermore, scSNViz conducts estimation, summary, and graphical representation of statistical metrics pertaining to sceSNVs distribution and expression across individual cells. It also provides support for the analysis of individual sceSNVs as well as sets comprising multiple expressed sceSNVs of interest.

Availability

ScSNViz is implemented as user-friendly R-scripts, freely available onhttps://horvathlab.github.io/NGS/scSNViz, supported by help utilities, and requiring no specialized bioinformatics skills for use.
Spatial chromosome organization and adaptation ofEscherichia coliunder heat stress
Authors: Wang Xu-Ting , Ma Bin-Guang
Published: June 2024

The spatial organization of bacterial chromosomes is crucial for cellular functions. It remains unclear how bacterial chromosomes adapt to high temperature stress. This study delves into the 3D genome architecture and transcriptomic responses ofEscherichia coliunder heat stress condition to unravel the intricate interplay between chromosome structure and environmental cues. By examining the role of macrodomains, chromosome interaction domains (CIDs), and nucleoid-associated proteins (NAPs), this work unveils the dynamic changes in chromosome conformation and gene expression patterns induced by high temperature stress. It was observed that under heat stress, short-range interaction frequency of chromosome decreased, while the long-range interaction frequency of the Ter macrodomain increased. Furthermore, two metrics, namely, Global Compactness (GC) and Local Compactness (LC), were devised to measure and compare the compactness of chromosomes based on their 3D structure models. The findings in this work shed light on the molecular mechanisms underlying thermal adaptation and chromosomal organization in bacterial cells, offering valuable insights into the complex interrelationships between environmental stimuli and genomic responses.
Spatial Deconvolution of Cell Types and Cell States at Scale Utilizing TACIT
Authors: Huynh Khoa L. A. , Tyc Katarzyna M. , Matuck Bruno F. , Easter Quinn T. , Pratapa Aditya , Kumar Nikhil V. , Pérez Paola , Kulchar Rachel , Pranzatelli Thomas , de Souza Deiziane , Weaver Theresa M. , Qu Xufeng , Alberto Valente Soares Junior Luiz , Dolhnokoff Marisa , Kleiner David E. , Hewitt Stephen M. , Fernando Ferraz da Silva Luiz , Rocha Vanderson Geraldo , Warner Blake M. , Byrd Kevin M. , Liu Jinze
Published: June 2024

Identifying cell types and states remains a time-consuming and error-prone challenge for spatial biology. While deep learning is increasingly used, it is difficult to generalize due to variability at the level of cells, neighborhoods, and niches in health and disease. To address this, we developed TACIT, an unsupervised algorithm for cell annotation using predefined signatures that operates without training data, using unbiased thresholding to distinguish positive cells from background, focusing on relevant markers to identify ambiguous cells in multiomic assays. Using five datasets (5,000,000-cells; 51-cell types) from three niches (brain, intestine, gland), TACIT outperformed existing unsupervised methods in accuracy and scalability. Integration of TACIT-identified cell with a novel Shiny app revealed new phenotypes in two inflammatory gland diseases. Finally, using combined spatial transcriptomics and proteomics, we discover under- and overrepresented immune cell types and states in regions of interest, suggesting multimodality is essential for translating spatial biology to clinical applications.