bluuebunny/crossref_metadata_2025 huggingface dataset:
Jeremian Scriptures in Exile
Authors: Goff Matthew
Published: July 2024

This chapter focuses on the book of Baruch and the Letter of Jeremiah. While very different texts, the history of the two books is intertwined; the Letter of Jeremiah has often been treated as the final chapter of Baruch. The figures of Baruch and Jeremiah are also related. In the Hebrew Bible, Baruch is the scribe of the prophet Jeremiah. The book of Baruch offers a plaintive account of the exiles in Babylon confessing their sins and renewing their commitment to follow the Torah. The book imagines a restored relationship between God and Israel by recounting the exiles returning to Jerusalem. The Letter of Jeremiah is presented as a letter written by Jeremiah to the exiles. Its overarching message is that the gods of the Babylonians are nothing but idols.
Judaism Offers the Best Path to Reason
Authors: Goff Matthew
Published: July 2024

This chapter offers an overview of 4 Maccabees which was considered a scriptural text by early Christians but is not in the canon of any faith community today. The composition seeks to demonstrate the supremacy of reason over the emotions and that Jewish tradition offers the best way to cultivate reason. The composition does so with an extensive retelling of the gruesome story of the death and torture of Eleazar, a mother, and her seven sons, found in 2 Maccabees 6–7. 4 Maccabees draws extensively on Greek philosophy, in particular the Stoic tradition, to present enduring torture and accepting death as the pinnacle of reason.
AUDIT C compared to PEth in middle-aged volunteers
Authors: Fredriksson Marie , Werner Mårten
Published: July 2024

Aims

To compare Alcohol Use Disorders Identification Test (AUDIT C) to phosphatidylethanol (PEth) in middle-aged randomly selected volunteers. Apply previously suggested lower cut-offs for PEth using moderate alcohol intake according to AUDIT C as a reference.

Methods

Within the Swedish CardioPulmonary BioImage Study, 2255 middle-aged (50–64 years of age) volunteers in northern Sweden participated in comparing AUDIT C to PEth 16:0/18:1.

Results

There was a moderate correlation between PEth 16:0/18:1 and AUDIT C (r = 0.66). None of the participants with the AUDIT C-score 0 had a measurable PEth. Of moderate alcohol consumers, according to AUDIT C (AUDIT C 1–3 women, 1–4 men), 96% had a PEth below 0.3 μmol/L, 91% had a PEth below 0.16 μmol/L, and 84% had a PEth below 0.11 μmol/L. With PEth equivalent to excessive alcohol consumption (≥0.3 μmol/L), 26% had an AUDIT C-score below excessive alcohol consumption (<4 for women and <5 for men). Thirty percent of patients with a PEth ≥0.16 μmol/L had an AUDIT C-score below excessive alcohol consumption, and 37% had a PEth ≥0.11 μmol/L. We found no significant correlation between BMI and PEth or AUDIT C.

Conclusions

There is a significant correlation between AUDIT C and PEth. Using AUDIT C alone, 26% of high-consumers, according to PEth, are not found in our cohort, but an AUDIT C-score of 0 will exclude high consumption, according to PEth. Our findings support the current cut-off for PEth of 0.3 μmol/L, but a lower cut-off seems reasonable.
2023 ESBRA Nordmann Award Lecture: Involvement of the gut microbiome-brain axis in alcohol use disorder
Authors: Leclercq Sophie
Published: July 2024

The human intestine is colonized by a variety of microorganisms that influence the immune system, the metabolic response, and the nervous system, with consequences for brain function and behavior. Unbalance in this microbial ecosystem has been shown to be associated with psychiatric disorders, and altered gut microbiome composition related to bacteria, viruses, and fungi has been well established in patients with alcohol use disorder. This review describes the gut microbiome–brain communication pathways, including the ones related to the vagus nerve, the inflammatory cytokines, and the gut-derived metabolites. Finally, the potential benefits of microbiota-based therapies for the management of alcohol use disorder, such as probiotics, prebiotics, and fecal microbiota transplantation, are also discussed.
Evaluation of the Impact of Physical Therapy on Patients With Macromastia Seeking Breast Reduction Surgery
Authors: McCranie Alec , Lee Anna D , Cyrus Chanise , Desjardins Haley , Winocour Julian , Mathes David , Kaoutzanis Christodoulos
Published: July 2024

Background

Macromastia significantly impairs females’ quality of life, with treatments such as physical therapy (PT) often providing only temporary relief. Insurance routinely denies breast reduction surgery, despite little relief after conservative treatments. Research on the efficacy of PT for macromastia is limited.

Objectives

In this study, we investigated the efficacy of PT for macromastia and identified patient factors associated with progression to surgery.

Methods

We conducted a retrospective cohort study of patients with macromastia between 2017 and 2021. We collected data on presenting symptoms, attempted conservative treatments, PT duration, and whether surgery was performed. All patients were invited to participate in a survey regarding their symptoms, treatments, and responses to treatments. Symptoms associated with patients progressing to a breast reduction were evaluated with a multiple logistic regression.

Results

Among the 327 patients identified with macromastia, 312 (95.41%) reported back pain and 272 (83.18%) attempted PT. Of the 72 (22.02%) patients who responded to the survey, 152 (46.48%) underwent subsequent surgery. The mean time from initial consultation to surgery was 283 days. Bra strap grooving was associated with progression to surgery (odds ratio = 1.90, CI = 1.02-3.54). Mean patient-reported pain levels decreased after surgery compared to after PT (pre-PT = 7.1, post-PT = 7.1, post-surgery = 3.1, P < .001).

Conclusions

Patients frequently undergo PT before breast reduction surgery despite no significant reduction in pain, whereas those who undergo surgery experience permanent relief and significantly reduced pain. Patients with bra strap grooving are more likely to progress to surgery. The requirement for PT as a prerequisite for surgery by insurance companies should be reevaluated.

Level of Evidence: 3
Evaluating the relationship between depression, suicidal thoughts and ulcerative colitis in patients with acne on isotretinoin: a case–control study
Authors: Verma Kritin K , Chiu Josephine , Connor Joshua , Khareedhi Aditi K , Panchal Smriti , Dhavala Maitreyi , Alamar Hayder , Ni Cynthia , Nepangue Jexy A , Tarbox Michelle B , Friedmann Daniel P
Published: July 2024

Our case–control study investigated the association between isotretinoin use and the incidence of depression, suicidal thoughts and ulcerative colitis among 14 365 patients with acne using the All of Us open-access database. The findings revealed no statistically significant correlation between isotretinoin use and these conditions, supporting the safety profile of isotretinoin in dermatological treatments.
Concurrent autoimmune blistering diseases in VEXAS syndrome: a report of two cases
Authors: Bao Aaron , Munjal Ananya , Reddy Pooja S , Park Eugene , Synkowski Daniel R , Jedrych Jaroslaw J , Kang Jun
Published: July 2024

VEXAS (vacuoles, E1-enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently characterized autoinflammatory condition driven by myeloid cell dysregulation. We report two patients with concurrent diagnoses of VEXAS syndrome and autoimmune blistering diseases – pemphigus vulgaris and dermatitis herpetiformis – highlighting a previously undescribed association between innate immune dysregulation and autoantibody-mediated skin diseases.
The functional connectivity between right insula and anterior cingulate cortex underlying the association between future self-continuity and delay discounting
Authors: Zhao Hengyue , Sun Jingjing , Zhang Rong , Jiang Yumeng , Zhang Yuetong , Feng Tingyong , Feng Pan
Published: July 2024

Delay discounting refers to the tendency of individuals to devalue future rewards as the delay in their receipt increases over time. Previous studies have indicated that future self-continuity correlates with delay discounting rates. However, the neural basis underlying the relationship between future self-continuity and delay discounting is not clear. To address this question, we used voxel-based morphometry and resting-state functional connectivity analyses to investigate the neural basis underlying the association between future self-continuity and delay discounting. Behavioral result showed that future self-continuity was positively associated with delay discounting. Voxel-based morphometry analysis result indicated that gray matter volume in the right dorsal anterior insula was positively correlated with future self-continuity. Resting-state functional connectivity analysis found that functional connectivity between the right dorsal anterior insula and anterior cingulate cortex was positively associated with future self-continuity. Mediation analysis showed that the right dorsal anterior insula–right anterior cingulate cortex functional connectivity partially mediated the relationship between future self-continuity and delay discounting. These results suggested that right dorsal anterior insula–right anterior cingulate cortex functional connectivity could be the neural basis underlying the association between future self-continuity and delay discounting. In summary, the study provided novel insights into how future self-continuity affected delay discounting and offers new explanations from a neural perspective.
Aggregation of positively charged poly(methyl methacrylate) latex particles in the presence of trifluoromethanesulfonate anion
Authors: Yamazaki Takashi , Tsuji Toshikazu
Published: July 2024

We investigated the unique aggregation behavior of 3 types of positively charged poly(methyl methacrylate) (PMMA) latex particles in the presence of a trifluoromethanesulfonate (triflate) anion. The particles were prepared based on surfactant-free emulsion polymerization using azo radical initiators. The triflate anion was strongly adsorbed to surfaces of positively charged PMMA latex particles, as confirmed by electrophoresis. Additionally, its presence significantly reduced the critical coagulation concentration of the cationic PMMA latex particles compared with other anions.
Synthesis of Pd–Pt–P amorphous nanoparticles
Authors: Ikeda Kenta , Mukoyoshi Megumi , Kusada Kohei , Yamamoto Tomokazu , Murakami Yasukazu , Kitagawa Hiroshi
Published: July 2024

Amorphous materials are very attractive materials because of their unique properties, including high corrosion resistance and catalytic activity. Creating such materials on a nanoscale is very effective in maximizing their performance. However, it is difficult to synthesize amorphous nanomaterials by conventional rapid cooling methods, commonly used for bulk amorphous materials. Therefore, there are not as many reports about amorphous nanomaterials as bulk materials. Herein we report the first synthesis of Pd–Pt–P amorphous nanoparticles by a 2-step synthesis method. They were also characterized.
Preliminary Findings From the Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE I) Study: A Randomized Controlled Trial
Authors: Cowling Benjamin J , Wong Sook-San , Santos Jefferson J S , Touyon Lisa , Ort Jordan T , Ye Naiqing , Kwok Natalie K M , Ho Faith , Cheng Samuel M S , Ip Dennis K M , Peiris Malik , Webby Richard J , Wilson Patrick C , Valkenburg Sophie A , Tsang John S , Leung Nancy H L , Hensley Scott E , Cobey Sarah
Published: July 2024

Background

Studies have reported that repeated annual vaccination may influence influenza vaccination effectiveness in the current season.

Methods

We established a 5-year randomized placebo-controlled trial of repeated influenza vaccination (Flublok; Sanofi Pasteur) in adults 18–45 years of age. In the first 2 years, participants were randomized to receive vaccine or saline placebo as follows: placebo-placebo (P-P), placebo-vaccine (P-V), or vaccine-vaccine (V-V). Serum samples were collected each year just before vaccination and after 30 and 182 days. A subset of serum samples collected at 5 time points from 95 participants were tested for antibodies against vaccine strains.

Results

From 23 October 2020 through 11 March 2021 we enrolled and randomized 447 adults. Among vaccinated individuals, antibody titers increased between days 0 and 30 against each of the vaccine strains, with smaller increases for repeat vaccinees who on average had higher prevaccination titers in year 2. There were statistically significant differences in the proportions of participants achieving ≥4-fold rises in antibody titer for the repeat vaccinees for influenza A(H1N1), B/Victoria, and B/Yamagata, but not for A(H3N2). Among participants who received vaccination in year 2, there were no significant differences between the P-V and V-V groups in geometric mean titers at day 30 or the proportions of participants with antibody titers ≥40 at day 30 for any of the vaccine strains.

Conclusions

In the first 2 years, during which influenza did not circulate, repeat and first-time vaccinees had similar postvaccination geometric mean titers to all 4 vaccine strains, indicative of similar levels of clinical protection.

Clinical Trials Registration. NCT04576377
Validating Combination Throat-Nasal Swab Specimens for Coronavirus Disease 2019 Tests Would Improve Early Detection, Especially for the Most Vulnerable
Authors: Viloria Winnett Alexander , Stenzel Timothy , Ismagilov Rustem F
Published: July 2024

Early detection of severe acute respiratory syndrome coronavirus 2 infection by diagnostic tests can prompt actions to reduce transmission and improve treatment efficacy, especially for vulnerable groups such as immunocompromised individuals. Recent evidence suggests that sampling the throat in addition to the nose improves clinical sensitivity during early infection for both antigen and molecular coronavirus disease 2019 tests. We urge test manufacturers to validate tests for use with throat swab, in combination with nasal swabs.
Long-term outcomes of high bleeding risk patients undergoing percutaneous coronary intervention: a Korean nationwide registry
Authors: Kang Jeehoon , Yun Junpil , Park Kyung Woo , Park Minae , Park Sojeong , Hwang Doyeon , Han Jung-Kyu , Yang Han-Mo , Kang Hyun-Jae , Koo Bon-Kwon , Angiolillo Dominick J , Urban Philip , Kim Hyo-Soo
Published: July 2024

Background and Aims

Patients with high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) are at increased risk of not only bleeding, but also ischaemic events. This study aimed to determine the long-term relative risk of ischaemic and bleeding events in HBR patients.

Methods

This study was a nationwide cohort study, based on the Korean National Health Insurance Review and Assessment Service database. Patients diagnosed with stable angina or acute coronary syndrome and those who underwent PCI in Korea between 2009 and 2018 were included in the analysis. According to the Academic Research Consortium HBR criteria, the total population was divided into HBR and non-HBR groups. The co-primary outcomes were major bleeding events and ischaemic (composite of cardiac death, myocardial infarction, and ischaemic stroke) events.

Results

Among a total of 325 417 patients who underwent PCI, 66 426 patients (20.4%) had HBR. During the follow-up period, HBR patients had a higher risk for major bleeding events (23.9% vs. 8.9%, P < .001) and ischaemic events (33.8% vs. 14.4%, P < .001). However, the impact of HBR was significant for major bleeding events [hazard ratio (HR) 3.12, 95% confidence interval (CI) 3.04–3.21, P < .001] and for ischaemic events (HR 2.50, 95% CI 2.45–2.56, P < .001). The HBR group was also associated with a greater risk of all-cause mortality (HR 3.73, 95% CI 3.66–3.79, P < .001). The average annual rate of major bleeding events within the first year after PCI was 5.5% for a single major criterion, and 2.9% for a single minor criterion.

Conclusions

Among patients undergoing PCI, those with HBR were at increased long-term risk for both bleeding and ischaemic events, with a greater risk of mortality compared to non-HBR patients.
Variation and Interaction of Distinct Subgenomes Contribute to Growth Diversity in Intergeneric Hybrid Fish
Authors: Ren Li , Luo Mengxue , Cui Jialin , Gao Xin , Zhang Hong , Wu Ping , Wei Zehong , Tai Yakui , Li Mengdan , Luo Kaikun , Liu Shaojun
Published: July 2024

Intergeneric hybridization greatly reshapes regulatory interactions among allelic and non-allelic genes. However, their effects on growth diversity remain poorly understood in animals. In this study, we conducted whole-genome sequencing and RNA sequencing analyses in diverse hybrid varieties resulting from the intergeneric hybridization of goldfish (Carassius auratus red var.) and common carp (Cyprinus carpio). These hybrid individuals were characterized by distinct mitochondrial genomes and copy number variations. Through a weighted gene correlation network analysis, we identified 3693 genes as candidate growth-regulating genes. Among them, the expression of 3672 genes in subgenome R (originating from goldfish) displayed negative correlations with body weight, whereas 20 genes in subgenome C (originating from common carp) exhibited positive correlations. Notably, we observed intriguing expression patterns of solute carrier family 2 member 12 (slc2a12) in subgenome C, showing opposite correlations with body weight that changed with water temperatures, suggesting differential interactions between feeding activity and weight gain in response to seasonal changes for hybrid animals. In 40.30% of alleles, we observed dominant trans-regulatory effects in the regulatory interactions between distinct alleles from subgenomes R and C. Integrating analyses of allele-specific expression and DNA methylation data revealed that DNA methylation on both subgenomes shaped the relative contribution of allelic expression to the growth rate. These findings provide novel insights into the interactions of distinct subgenomes that underlie heterosis in growth traits and contribute to a better understanding of multiple allelic traits in animals.
Mutation of YFT3, an isomerase in the isoprenoid biosynthetic pathway, impairs its catalytic activity and carotenoid accumulation in tomato fruit
Authors: Li Wenzhen , Chen Lulu , Zhao Weihua , Li Yuhang , Chen Ying , Wen Tengjian , Liu Zhengjun , Huang Chao , Zhang Lida , Zhao Lingxia
Published: July 2024

Tomato fruit colors are directly associated with their appearance quality and nutritional value. However, tomato fruit color formation is an intricate biological process that remains elusive. In this work we characterized a tomato yellow fruited tomato 3 (yft3, e9292, Solanum lycopersicum) mutant with yellow fruits. By the map-based cloning approach, we identified a transversion mutation (A2117C) in the YFT3 gene encoding a putative isopentenyl diphosphate isomerase (SlIDI1) enzyme, which may function in the isoprenoid biosynthetic pathway by catalyzing conversion between isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). The mutated YFT3 (A2117C) (designated YFT3 allele) and the YFT3 genes did not show expression difference at protein level, and their encoded YFT3 allelic (S126R) and YFT3 proteins were both localized in plastids. However, the transcript levels of eight genes (DXR, DXS, HDR, PSY1, CRTISO, CYCB, CYP97A, and NCED) associated with carotenoid synthesis were upregulated in fruits of both yft3 and YFT3 knockout (YFT3-KO) lines at 35 and 47 days post-anthesis compared with the red-fruit tomato cultivar (M82). In vitro and in vivo biochemical analyses indicated that YFT3 (S126R) possessed much lower enzymatic activities than the YFT3 protein, indicating that the S126R mutation can impair YFT3 activity. Molecular docking analysis showed that the YFT3 allele has higher ability to recruit isopentenyl pyrophosphate (IPP), but abolishes attachment of the Mg2+ cofactor to IPP, suggesting that Ser126 is a critical residue for YTF3 biochemical and physiological functions. As a result, the yft3 mutant tomato line has low carotenoid accumulation and abnormal chromoplast development, which results in yellow ripe fruits. This study provides new insights into molecular mechanisms of tomato fruit color formation and development.
Local and systemic transcriptome and spliceome reprogramming induced by the root-knot nematode Meloidogyne incognita in tomato
Authors: Ozdemir Selin , Piya Sarbottam , Lopes-Caitar Valeria S , Coffey Nicole , Rice J Hollis , Hewezi Tarek
Published: July 2024

Root-knot nematodes (Meloidogyne spp.) are widely spread root parasites that infect thousands of vascular plant species. These highly polyphagous nematodes engage in sophisticated interactions with host plants that results in the formation of knot-like structures known as galls whose ontogeny remains largely unknown. Here, we determined transcriptome changes and alternative splicing variants induced by Megalaima incognita in galls and neighboring root cells at two distinct infective stages. M. incognita induced substantial transcriptome changes in tomato roots both locally in galls and systemically in neighboring cells. A considerable parallel regulation of gene expression in galls and neighboring cells were detected, indicative of effective intercellular communications exemplified by suppression of basal defense responses particularly during the early stage of infection. The transcriptome analysis also revealed that M. incognita exerts a tight control over the cell cycle process as a whole that results in an increase of ploidy levels in the feeding sites and accelerated mitotic activity of the gall cells. Alternative splicing analysis indicated that M. incognita significantly modulates pre-mRNA splicing as a total of 9064 differentially spliced events from 2898 genes were identified where intron retention and exon skipping events were largely suppressed. Furthermore, a number of differentially spliced events were functionally validated using transgenic hairy root system and found to impact gall formation and nematode egg mass production. Together, our data provide unprecedented insights into the transcriptome and spliceome reprogramming induced by M. incognita in tomato with respect to gall ontogeny and nematode parasitism.
A question-answering framework for automated abstract screening using large language models
Authors: Akinseloyin Opeoluwa , Jiang Xiaorui , Palade Vasile
Published: July 2024

Objective

This paper aims to address the challenges in abstract screening within systematic reviews (SR) by leveraging the zero-shot capabilities of large language models (LLMs).

Methods

We employ LLM to prioritize candidate studies by aligning abstracts with the selection criteria outlined in an SR protocol. Abstract screening was transformed into a novel question-answering (QA) framework, treating each selection criterion as a question addressed by LLM. The framework involves breaking down the selection criteria into multiple questions, properly prompting LLM to answer each question, scoring and re-ranking each answer, and combining the responses to make nuanced inclusion or exclusion decisions.

Results and Discussion

Large-scale validation was performed on the benchmark of CLEF eHealth 2019 Task 2: Technology-Assisted Reviews in Empirical Medicine. Focusing on GPT-3.5 as a case study, the proposed QA framework consistently exhibited a clear advantage over traditional information retrieval approaches and bespoke BERT-family models that were fine-tuned for prioritizing candidate studies (ie, from the BERT to PubMedBERT) across 31 datasets of 4 categories of SRs, underscoring their high potential in facilitating abstract screening. The experiments also showcased the viability of using selection criteria as a query for reference prioritization. The experiments also showcased the viability of the framework using different LLMs.

Conclusion

Investigation justified the indispensable value of leveraging selection criteria to improve the performance of automated abstract screening. LLMs demonstrated proficiency in prioritizing candidate studies for abstract screening using the proposed QA framework. Significant performance improvements were obtained by re-ranking answers using the semantic alignment between abstracts and selection criteria. This further highlighted the pertinence of utilizing selection criteria to enhance abstract screening.
Electronic documentation burden among outpatient rehabilitation therapists: a qualitative descriptive study and quality improvement initiative
Authors: Schwartz-Dillard Jessica , Ng Travis , Villegas Joann , Johnson Derrick , Murray-Weir Mary
Published: July 2024

Objectives

Outpatient rehabilitation (rehab) physical, occupational, and speech therapists use electronic health records (EHR), yet their documentation experiences, including any documentation burden, are not well researched. Therapists are a growing portion of the U.S. healthcare workforce, whose need is critical to the health of an aging population. We aimed to describe outpatient rehab therapists’ documentation experiences and identify strategies for mitigating any documentation burden.

Materials and Methods

We used qualitative descriptive methodology to conduct 4 focus groups with outpatient rehab therapists at Hospital for Special Surgery, a multi-site orthopedic institution. Transcripts were inductively coded to identify themes and actionable strategies for improving the therapists’ documentation experiences. Therapists provided feedback and prioritization of proposed strategies.

Results

A total of 13 therapists were interviewed. Five themes and 10 subthemes characterize the therapists’ documentation experience by a feeling that documentation inhibits clinical care and work/life balance, a perceived lack of support and efficiencies, the desire to document to communicate clinical care, and a design vision for improving the EHR. Top prioritized strategies for improvement included use of timesaving templates, expanding dictation, decluttering the EHR interface, and support for free texting over discrete data capture.

Discussion

Outpatient rehab therapists experience documentation burden similar to that documented of physicians and nurses. Manual data entry imposes burden on therapists’ time and clinical care.

Conclusion

A multi-faceted approach is needed for improving therapists’ experiences including EHR redesign, technology supporting dictation and narrative to discrete data capture, and support from leadership and regulators.
Opportunistic Infections, Mortality Risk, and Prevention Strategies in Patients With Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic (VEXAS) Syndrome
Authors: Czech Mary , Cuellar-Rodriguez Jennifer , Patel Bhavisha A , Groarke Emma M , Cowen Edward W , Turturice Benjamin , Beck David B , Wilson Lorena , Goodspeed Wendy , Darden Ivana , Young Neal S , Hickstein Dennis , Ombrello Amanda , Hoffman Patrycjia , Arikan Evsen Apaydin , Sinaii Ninet , Hathaway Londa , Castelo-Soccio Leslie , Fike Alice , Kastner Daniel B , Grayson Peter C , Ferrada Marcela A
Published: July 2024

Background

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a genetic disorder characterized by bone marrow failure and systemic inflammation, putting patients at risk for infections. This study comprehensively examines the prevalence of opportunistic infections in patients with VEXAS, evaluating their impact on clinical outcomes and potential preventive measures.

Methods

Patients with confirmed VEXAS were included. Survival analysis and logistic regression were used to identify associations between opportunistic infections and mortality. Infection rates (IRs) for Pneumocystis jirovecii pneumonia (PJP) and alphaherpesviruses were calculated over a prospective 8-month observation period in relationship to prophylaxis.

Results

Of 94 patients with VEXAS, 6% developed PJP; 15% had alphaherpesvirus reactivation, with varicella zoster virus (VZV) being the most common herpesvirus; and 10% contracted a nontuberculous mycobacterial (NTM) infection. Risk of death was significantly increased per month following a diagnosis of PJP (hazard ratio [HR], 72.41 [95% confidence interval {CI}, 13.67–533.70]) or NTM (HR, 29.09 [95% CI, 9.51–88.79]). Increased odds for death were also observed in patients with a history of herpes simplex virus (HSV) reactivation (odds ratio [OR], 12.10 [95% CI, 1.29–114.80]) but not in patients with VZV (OR, 0.89 [95% CI, .30–2.59]). Prophylaxis for PJP (IR, 0.001 vs 0 per person-day, P < .01) and VZV (IR, 0.006 vs 0 per person-day, P = .04) markedly decreased infection rates with a number needed to treat of 4 and 7, respectively.

Conclusions

Opportunistic infections are common in patients with VEXAS. Patients who develop PJP, HSV, or NTM are at increased risk for death. Prophylaxis against PJP and VZV is highly effective.
GMP-compliant iPS cell lines show widespread plasticity in a new set of differentiation workflows for cell replacement and cancer immunotherapy
Authors: Terheyden-Keighley Daniel , Hühne Melanie , Berger Thomas , Hiller Björn , Martins Soraia , Gamerschlag Anna , Sabour Davood , Meffert Andrea , Kislat Andreas , Slotta Carsten , Hafezi Francois , Lichte Jens , Sudheer Smita , Tessmer Karen , Psathaki Katherina , Ader Marius , Kogler Gesine , Greber Boris
Published: July 2024

Cell therapeutic applications based on induced pluripotent stem cells (iPSCs) appear highly promising and challenging at the same time. Good manufacturing practice (GMP) regulations impose necessary yet demanding requirements for quality and consistency when manufacturing iPSCs and their differentiated progeny. Given the scarcity of accessible GMP iPSC lines, we have established a corresponding production workflow to generate the first set of compliant cell banks. Hence, these lines met a comprehensive set of release specifications and, for instance, displayed a low overall mutation load reflecting their neonatal origin, cord blood. Based on these iPSC lines, we have furthermore developed a set of GMP-compatible workflows enabling improved gene targeting at strongly enhanced efficiencies and directed differentiation into critical cell types: A new protocol for the generation of retinal pigment epithelium (RPE) features a high degree of simplicity and efficiency. Mesenchymal stromal cells (MSCs) derived from iPSCs displayed outstanding expansion capacity. A fully optimized cardiomyocyte differentiation protocol was characterized by a particularly high batch-to-batch consistency at purities above 95%. Finally, we introduce a universal immune cell induction platform that converts iPSCs into multipotent precursor cells. These hematopoietic precursors could selectively be stimulated to become macrophages, T cells, or natural killer (NK) cells. A switch in culture conditions upon NK-cell differentiation induced a several thousand-fold expansion, which opens up perspectives for upscaling this key cell type in a feeder cell-independent approach. Taken together, these cell lines and improved manipulation platforms will have broad utility in cell therapy as well as in basic research.
Genetically Similar Xanthomonas arboricola pv. pruni Strains and Associated Phages Display Phenotypic and Genotypic Variation Across 35 Years
Authors: D'Amico-Willman Katherine M. , Joglekar Prasanna , Ritchie David F. , Smith Amber M. , Heiberger Helena , Huerta Alejandra I.
Published: July 2024

Bacteriophages (phages), viruses that infect bacteria, have key ecological and evolutionary functions in the phytobiome. Despite the importance of phages as primary drivers for bacterial evolution, phage-bacteria interactions across spatiotemporal scales in natural, agricultural settings are underexplored. With increased interest in phage-based therapies to manage bacterial pathogens, an enhanced understanding of phage genetic and functional diversity at the population level and how this, in turn, impacts bacterial evolution and virulence, is necessary. This study presents data on the genetic similarity among Xanthomonas arboricola pv. pruni (Xap) strains isolated from different geographic locations that display different lytic phenotypes when challenged with a panel of six phage isolates collected in the same region over four decades. The minor yet significant genetic variation among this small population of Xap strains is structured by both geographic location and response to phage infection. Phage genomes are also highly similar, with conserved and diverse genomic loci that correspond to isolation year. The six phages characterized here cluster into the Kantovirinae subfamily and possibly form a new genus. Only future studies will elucidate the role of Xap and Xapφ phage genes identified here in the virulence and lysis of Xap and how these, in turn, impact bacterial spot disease outcomes. The research and tripartite pathosystem presented here provide a unique opportunity to investigate the coevolution of phage-phytobacterial pathogen-plant host in depth in an agricultural setting with the potential to monitor the rate at which phage populations contribute to bacterial genetic diversity across geographic and temporal scales.

[Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Cardiac diastolic dysfunction by cigarette smoking is associated with mitochondrial integrity in the heart
Authors: Slotabec Lily , Wang Hao , Seale Blaise , Wen Changhong , Filho Fernanda , Li Ji
Published: July 2024

Cigarette smoking behaviors are harmful and cause one out of ten deaths due to cardiovascular disease. As population sizes grow and number of cigarette smokers increases, it is vital that we understand the mechanisms leading to heart failure in cigarette smokers. We have reported that metabolic regulation of a histone deacetylase, SIRT1, modulates cardiovascular and mitochondrial function under stress. Given this conclusion, we hypothesized that chronic cigarette smoking led to cardiovascular dysfunction via a reduction SIRT1. Mice were randomly organized into smoking or nonsmoking groups, and the smoking group received cigarette smoke exposure for 16 weeks. Following 16‐week exposure, diastolic function of the heart was impaired in the smoking group as compared to sham, indicated by a significant increase in E/e’. The electrical function of the heart was also impaired in the smoking group compared to the sham group, indicated by increased PR interval and decreased QTc interval. This diastolic dysfunction was not accompanied by increased fibrosis in mouse hearts, although samples from human chronic smokers indicated increased fibrosis compared to their nonsmoker counterparts. As well as diastolic dysfunction, mitochondria from the 16‐week smoking group showed significantly impaired function, evidenced by significant decreases in all parameters measured by the mitochondrial stress test. We further found biochemical evidence of a significantly decreased level of SIRT1 in left ventricles of both mouse and human smoking groups compared to nonsmoking counterparts. Data from this study indicate that decreased SIRT1 levels by cigarette smoking are associated with diastolic dysfunction caused by compromised mitochondrial integrity.
Beneficial Effect of Calcium Treatment for Hyperkalemia Is Not Due to “Membrane Stabilization”*
Authors: Piktel Joseph S. , Wan Xiaoping , Kouk Shalen , Laurita Kenneth R. , Wilson Lance D.
Published: July 2024

OBJECTIVES:

Hyperkalemia is a common life-threatening condition causing severe electrophysiologic derangements and arrhythmias. The beneficial effects of calcium (Ca2+) treatment for hyperkalemia have been attributed to “membrane stabilization,” by restoration of resting membrane potential (RMP). However, the underlying mechanisms remain poorly understood. Our objective was to investigate the mechanisms underlying adverse electrophysiologic effects of hyperkalemia and the therapeutic effects of Ca2+ treatment.

DESIGN:

Controlled experimental trial.

SETTING:

Laboratory investigation.

SUBJECTS:

Canine myocytes and tissue preparations.

INTERVENTIONS AND MEASUREMENTS:

Optical action potentials and volume averaged electrocardiograms were recorded from the transmural wall of ventricular wedge preparations (n = 7) at baseline (4 mM potassium), hyperkalemia (8–12 mM), and hyperkalemia + Ca2+ (3.6 mM). Isolated myocytes were studied during hyperkalemia (8 mM) and after Ca2+ treatment (6 mM) to determine cellular RMP.

MAIN RESULTS:

Hyperkalemia markedly slowed conduction velocity (CV, by 67% ± 7%; p < 0.001) and homogeneously shortened action potential duration (APD, by 20% ± 10%; p < 0.002). In all preparations, this resulted in QRS widening and the “sine wave” pattern observed in severe hyperkalemia. Ca2+ treatment restored CV (increase by 44% ± 18%; p < 0.02), resulting in narrowing of the QRS and normalization of the electrocardiogram, but did not restore APD. RMP was significantly elevated by hyperkalemia; however, it was not restored with Ca2+ treatment suggesting a mechanism unrelated to “membrane stabilization.” In addition, the effect of Ca2+ was attenuated during L-type Ca2+ channel blockade, suggesting a mechanism related to Ca2+-dependent (rather than normally sodium-dependent) conduction.

CONCLUSIONS:

These data suggest that Ca2+ treatment for hyperkalemia restores conduction through Ca2+-dependent propagation, rather than restoration of membrane potential or “membrane stabilization.” Our findings provide a mechanistic rationale for Ca2+ treatment when hyperkalemia produces abnormalities of conduction (i.e., QRS prolongation).
Risk Factors for Upper Extremity Impairment after Mastectomy: A Single Institution Retrospective Review
Authors: Carr Hannah M. , Patel Ronak A. , Beederman Maureen R. , Maassen Nicholas H. , Hanson Summer E.
Published: July 2024

Background:

Patients with breast cancer treated with mastectomy are more likely to develop upper extremity dysfunction compared with those treated with breast-conserving therapy. This study aimed to identify cancer and treatment characteristics that may be risk factors for development of upper extremity dysfunction in patients treated with mastectomy.

Methods:

The authors performed a retrospective chart review of patients at the University of Chicago who were treated with a unilateral or bilateral mastectomy from 2010 to 2020 and developed upper extremity dysfunction based on International Classification of Disease-10 codes. Patients were analyzed by side of body (left or right). Patient demographics and treatment characteristics were extracted from the electronic medical record.

Results:

In total, 259 patients met criteria and were included in our study. A total of 396 upper extremities were recorded as experiencing dysfunction and were analyzed. Mean age was 60 years (range = 28–96), and mean body mass index was 28.4 (SD = 7.5). An estimated 54% of patients underwent breast reconstruction. After multivariable analysis, chronic upper extremity pain was found to be associated with ipsilateral radiotherapy (P < 0.001) and ipsilateral in situ cancer (0.041). Limited range of motion was found to be associated with ipsilateral invasive cancer (P = 0.01), any ipsilateral mastectomy surgery (P < 0.001), and ipsilateral radiotherapy (P = 0.03). Musculoskeletal dysfunction was found to be associated with no ipsilateral modified radical mastectomy (P = 0.033). No oncological or treatment characteristics were found to be associated with decreased strength or adhesive capsulitis. Furthermore, breast reconstruction (implant or autologous tissue based) was not associated with upper extremity dysfunction.

Conclusion:

Breast cancer characteristics and treatment modalities may predispose patients treated with mastectomy to developing types of upper extremity dysfunction.
Effects of brain estrogen receptor on depression and its mechanism of action
Authors: Wen Yunran , Gao Kun , Tong Ge , Meng Xiaoying , Pan Mingmin , Wang Ying , Meng Danhua , Yu Zheng , Yue Guangxin
Published: July 2024

Depression is a refractory disease involving multiple pathologic changes, characterized by long-term disease course, low curative rate, and complex symptoms. However, the pathologic mechanism of this disease is incompletely known. Current research mainly focuses on the monoamine neurotransmitter hypothesis, neuroendocrine-related hypothesis, neuroinflammation hypothesis, and brain structure-function hypothesis. An intimate interplay exists between estrogen with the development and progression of depression. Estrogen receptors are widely distributed in the central nervous system, the expression of which can exert genetic and nongenetic effects to improve depression through regulating the level of neurotransmitters, mediating the function of the hypothalamus-pituitarium-adrenal axis, alleviating neuroinflammation, and protecting neurons. This study elaborated on the regulatory effect and mechanism of brain estrogen receptors on depression, hoping to provide new ideas for the clinical treatment of depression.
Current research situation analysis and strategic suggestions on the standardization of materia medica literature based on ancient books
Authors: Wang Wanbing , Yu Qiuhui , Yu Zheng , Du Song
Published: July 2024

Materia medica literature is a vital carrier for materia medica research. The standardization of research on materia medica literature is an important prerequisite and a key link in the process of digging and sorting out materia medica literature. Currently, some research regarding literature of materia medica ancient books has the property of standardization, and corresponds with the core concept of traditional Chinese medicine standardization. This study systematically collated the ancient books with a standardized nature of materia medica literature throughout history, and deeply summarized the current research situation analysis of materia medica literature with a standardized nature, based on the brief exploration against the significance of standardization in materia medica literature. Accordingly, further analyses were conducted on the limitation of the preliminary exploration of materia medica literature standardization based on ancient books, in an attempt to provide strategic suggestions for future work on materia medica literature standardization, and promote the scientific, normalized, and standardized development of materia medica research.
Frequency and Outcome of Emergency Penetrating Keratoplasty in Infectious Keratitis in Sweden During the 21st Century
Authors: Viberg Andreas , Byström Berit
Published: July 2024

Purpose:

To study the frequency over time and outcome of penetrating keratoplasty (PK), “keratoplasty à chaud,” in patients with infectious keratitis with 2-year follow-up data.

Methods:

This register-based study included keratitis cases that had undergone PK in Sweden between 2001 and 2020 and reported to the Swedish Corneal Transplant Register.

Results:

During the study period, 69 eyes were subjected to acute PK due to progressive infectious keratitis. The number increased from 2 annual procedures in the first half of the study period to 5 in the second half (P = 0.01). Preoperative corneal perforation was present in 43.5% (n = 30) of the eyes. Two years after surgery, follow-up data were completed in the register for 53 eyes; of these, 62.3% (n = 33) were considered to have functioning grafts, and 20.8% (n = 11) had experienced a rejection episode. The visual acuity improved from hand motion to counting fingers (P = 0.002), and the proportion of eyes with a visual acuity of ≤1.0 logMAR increased from 5.7% (n = 3) before the surgery to 45.3% (n = 24) at the 2-year follow-up (P < 0.001).

Conclusions:

The number of active infectious keratitis cases undergoing keratoplasty à chaud increased in Sweden during the 21st century. Most of the cases were successful regarding the structural integrity of the bulb, that is, “had a saved eye” and even a functioning graft 2 years after corneal transplantation. The visual gain was distinct, albeit modest. In cases with severe infectious keratitis, and even a concomitant perforation in the cornea due to the infection, corneal transplantation should continue to be an option.
Management of vitreous floaters: a review
Authors: Aleman Alexis Ivan , Kiryakoza Lauren , Sridhar Jayanth , Sengillo Jesse
Published: July 2024

Purpose of review

Vitreous floaters, characterized by the perception of spots or shadows in the visual field, commonly result from posterior vitreous detachment and can cause chronic symptoms in affected patients. The diagnosis of posterior vitreous detachment is typically determined clinically and can sometimes be confirmed with optical coherence topography (OCT) [1▪▪]. The objective of this review is to review management options for symptomatic vitreous floaters.

Recent findings

Symptoms of vitreous floaters may be mild or may significantly affect patient quality of life. Observation is the most common management strategy. Procedural management options include pars plana vitrectomy (PPV) and neodymium-doped yttrium aluminium garnet (Nd:YAG) vitreolysis. PPV is considered the most definitive management option for vitreous floaters. PPV, however, carries inherent risks, notably infection, cataract formation, and retinal detachment [2]. Nd:YAG laser vitreolysis is a less invasive alternative with studies demonstrating varied success [1▪▪,3,4].

This review provides insights into the current state of knowledge regarding the management of vitreous floaters and can guide clinical decision-making.
Immune recovery uveitis: an ocular manifestation in HIV/AIDS receiving treatment
Authors: Dionson Martin M.
Published: July 2024

Purpose of review

This article intends to briefly discuss AIDS, summarize the current literature on immune recovery uveitis, describe its ocular manifestations and complications, and tackle its complex management.

Recent findings

The clinical picture of immune recovery uveitis is still evolving. Up to today, there are still no definite criteria for immune recovery uveitis, and although closely associated with cytomegalovirus retinitis and HIV/AIDS, there are several cases of similar intraocular response in non-HIV patients. The exact pathology for this paradoxical inflammatory reaction remains unclear; however, there is an interest in identifying biomarkers to determine underlying mechanisms and identify patients at risk. The management of this disease also remains a challenge and no standardized treatment approach exists currently.

Immune recovery uveitis is an important cause of visual morbidity particularly in HIV/AIDS patients receiving highly active antiretroviral. It is a paradoxical reaction that is frequently associated with a prior cytomegalovirus retinitis infection. Although it can be a transient and self-limiting process, there is a complex decision on the timing of antiviral treatment and the initiation of antiretroviral treatment to prevent immune recovery uveitis. Furthermore, a substantial challenge arises in balancing

treatment decisions for complications in refractory cases.