bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long COVID and post‐acute sequelae of SARS‐CoV‐2 pathogenesis and treatment: A Keystone Symposia report
Authors: Durstenfeld Matthew S. , Weiman Shannon , Holtzman Michael , Blish Catherine , Pretorius Resia , Deeks Steven G. 
Published: April 2024

AbstractIn 2023, the Keystone Symposia held the first international scientific conference convening research leaders investigating the pathology of post‐acute sequelae of COVID‐19 (PASC) or Long COVID, a growing and urgent public health priority. In this report, we present insights from the talks and workshops presented during this meeting and highlight key themes regarding what researchers have discovered regarding the underlying biology of PASC and directions toward future treatment. Several themes have emerged in the biology, with inflammation and other immune alterations being the most common focus, potentially related to viral persistence, latent virus reactivation, and/or tissue damage and dysfunction, especially of the endothelium, nervous system, and mitochondria. In order to develop safe and effective treatments for people with PASC, critical next steps should focus on the replication of major findings regarding potential mechanisms, disentangling pathogenic mechanisms from downstream effects, development of cellular and animal models, mechanism‐focused randomized, placebo‐controlled trials, and closer collaboration between people with lived experience, scientists, and other stakeholders. Ultimately, by learning from other post‐infectious syndromes, the knowledge gained may help not only those with PASC/Long COVID, but also those with other post‐infectious syndromes.
Osteoradionecrosis incidence in pre‐radiation teeth extractions: A prospective study
Authors: Rupe C. , Gioco G. , Massaccesi M. , Tagliaferri L. , Pastore F. , Micciché F. , Galli J. , Mele D. , Specchia M. L. , Cassano A. , Cordaro M. , Lajolo C. 
Published: April 2024

AbstractAimsTo evaluate osteoradionecrosis (ORN) incidence in a cohort of patients undergoing tooth extraction (TE) before radiotherapy (RT) for head and neck cancers.MethodsThe study protocol was approved by the Ethics Committee of Università Cattolica del Sacro Cuore (ID‐2132) and registered at clinicaltrials.gov (ID: NCT04009161). TE was performed in case of signs of pericoronitis, periapical lesions, restorative impossibility, severe periodontitis. ORN was defined as exposed bone at an unhealed post‐extraction socket in the absence of oncological recurrence. The RT plans were reviewed, and each post‐extractive socket was contoured to calculate the received radiation dose.ResultsIn total, 156 patients with 610 TE were enrolled. The mean follow‐up was 567 days. ORN was diagnosed in four patients (2.6% of patients and 0.7% of TE). Need for osteotomy and radiation dose at the extraction site were associated with ORN (OR for osteotomy: 21.9, 95% CI: 2.17–222.2, p = 0.009; OR for RT dose: 1.1, 95% CI: 1–1.15, p = 0.05).ConclusionsTE appears to be a significant risk factor for ORN, particularly when osteotomy is required, and post‐extraction sockets receive a high RT dosage. This study proposes a decision‐making algorithm for TE and outlines a straightforward surgical protocol.
Understanding exosomes: Part 2—Emerging leaders in regenerative medicine
Authors: Miron Richard J. , Estrin Nathan E. , Sculean Anton , Zhang Yufeng 
Published: April 2024

AbstractExosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of diseases/conditions. Over 5000 publications are currently being published yearly on this topic, and this number is only expected to dramatically increase as novel therapeutic strategies continue to be developed. Today exosomes have been applied in numerous contexts including neurodegenerative disorders (Alzheimer's disease, central nervous system, depression, multiple sclerosis, Parkinson's disease, post‐traumatic stress disorders, traumatic brain injury, peripheral nerve injury), damaged organs (heart, kidney, liver, stroke, myocardial infarctions, myocardial infarctions, ovaries), degenerative processes (atherosclerosis, diabetes, hematology disorders, musculoskeletal degeneration, osteoradionecrosis, respiratory disease), infectious diseases (COVID‐19, hepatitis), regenerative procedures (antiaging, bone regeneration, cartilage/joint regeneration, osteoarthritis, cutaneous wounds, dental regeneration, dermatology/skin regeneration, erectile dysfunction, hair regrowth, intervertebral disc repair, spinal cord injury, vascular regeneration), and cancer therapy (breast, colorectal, gastric cancer and osteosarcomas), immune function (allergy, autoimmune disorders, immune regulation, inflammatory diseases, lupus, rheumatoid arthritis). This scoping review is a first of its kind aimed at summarizing the extensive regenerative potential of exosomes over a broad range of diseases and disorders.
A milestone in the pursuit of gender equality: Predicting first women presidents in U.S. higher education institutions, 1980–2018
Authors: D’Apice Hannah K. , Song Jieun , Wotipka Christine Min 
Published: April 2024

AbstractWhile women’s higher education enrollments and graduation rates have outpaced those of men in the United States and most countries around the world, women are less frequently included in academic leadership roles, including the higher education presidency. This paper asks what predicts whether and when a higher education institution has its first woman president, conceptualizing this event as a milestone of gender equality. We use a national probability sample of 234 four‐year U.S. universities and colleges, constructing a novel longitudinal dataset from 1980 to 2018. Employing event history analysis, we examine the potential mechanisms associated with when an institution has its first woman president over time. Our findings suggest that the demographic diversity of faculty and students, gender‐ and diversity‐supportive structures, and the broader environment in which institutions are embedded predict the likelihood that a woman will advance to the level of the presidency. In particular, the presence of gender studies programs and a higher proportion of women in state legislatures increase the likelihood that an institution will have its first woman president. At a time of growing challenges facing U.S. higher education, coupled with greater opportunities from having more diverse students and faculty, universities and colleges increasingly recognize the benefit of women leaders.
Spliceosomal complex components are critical for adjusting the C:N balance during high‐light acclimation
Authors: Araguirang Gali Estopare , Venn Benedikt , Kelber Nadja‐Magdalena , Feil Regina , Lunn John , Kleine Tatjana , Leister Dario , Mühlhaus Timo , Richter Andreas S. 
Published: April 2024

SUMMARYPlant acclimation to an ever‐changing environment is decisive for growth, reproduction, and survival. Light availability limits biomass production on both ends of the intensity spectrum. Therefore, the adjustment of plant metabolism is central to high‐light (HL) acclimation, and the accumulation of photoprotective anthocyanins is commonly observed. However, mechanisms and factors regulating the HL acclimation response are less clear. Two Arabidopsis mutants of spliceosome components exhibiting a pronounced anthocyanin overaccumulation in HL were isolated from a forward genetic screen for new factors crucial for plant acclimation. Time‐resolved physiological, transcriptome, and metabolome analysis revealed a vital function of the spliceosome components for rapidly adjusting gene expression and metabolism. Deficiency of INCREASED LEVEL OF POLYPLOIDY1 (ILP1), NTC‐RELATED PROTEIN1 (NTR1), and PLEIOTROPIC REGULATORY LOCUS1 (PRL1) resulted in a marked overaccumulation of carbohydrates and strongly diminished amino acid biosynthesis in HL. While not generally limited in N‐assimilation, ilp1, ntr1, and prl1 showed higher glutamate levels and reduced amino acid biosynthesis in HL. The comprehensive analysis reveals a function of the spliceosome components in the conditional regulation of the carbon:nitrogen balance and the accumulation of anthocyanins during HL acclimation. The importance of gene expression, metabolic regulation, and re‐direction of carbon towards anthocyanin biosynthesis for HL acclimation are discussed.
Short‐term outcomes of 43 dogs treated with arthroscopic suturing for meniscal tears associated with cranial cruciate ligament disease
Authors: Rocheleau Patrick J. , Robson Alexandria , Bird Sarah D. , Pickersgill Megan M. , Holz Kali A. 
Published: April 2024

AbstractObjectiveTo describe short‐term outcomes and complications in dogs receiving meniscal suturing and concurrent tibial plateau leveling osteotomy (TPLO) with or without augmentation with an extracapsular suture.Study designRetrospective case series.AnimalsForty‐three client‐owned dogs submitted for cruciate ligament disease.MethodsDogs were included if meniscal suturing was performed during or after a TPLO procedure. Criteria included an unstable medial meniscus without evidence of a tear, a caudal vertical longitudinal tear with or without displacement, or if a bucket‐handle tear was debrided and the remaining rim was unstable. Stifle stabilization was performed by either a standard TPLO or an augmented TPLO (TPLO + internal brace [IB]). Outcome measures included physical examination findings, radiographs, subjective gait examination, Liverpool Osteoarthritis in Dogs (LOAD) scores, and second‐look arthroscopy.ResultsForty‐four meniscal repairs were performed in 43 dogs. Five types of meniscal tears were treated employing eight suture materials. Complications were documented in 15 cases (34%). The stabilization technique had a significant impact on the outcome (p = .049): TPLO + IB had a 93.3% success rate and the success rate was 71.4% in the TPLO‐only group.ConclusionFive types of meniscal pathology were addressed successfully in the study, indicating that currently accepted criteria for meniscal suturing in dogs may be overly conservative. The majority of complications were not related to the meniscal suturing itself and did not compromise the outcome. The stifle stabilization technique had an impact on outcome.Clinical significanceThe authors found arthroscopic meniscal suturing to be practical and successful in this patient population. Postoperative stifle stability had an impact on successful treatment.
Effective Stretching Positions of the Piriformis Muscle Evaluated Using Shear Wave Elastography
Authors: Itsuda Hikari , Yagi Masahide , Yanase Ko , Umehara Jun , Mukai Hiyu , Ichihashi Noriaki 
Published: April 2024

Context: Piriformis syndrome is often associated with muscle spasms and shortening of the piriformis muscle (PM). Physical therapy, including static stretching of the PM, is one of the treatments for this syndrome. However, the effective stretching position of the PM is unclear in vivo. This study aimed to determine the effective stretching positions of the PM using ultrasonic shear wave elastography. Design: Observational study. Methods: Twenty-one healthy young men (22.7 [2.4] y) participated in this study. The shear elastic modulus of the PM was measured at 12 stretching positions using shear wave elastography. Three of the 12 positions were tested with maximum internal rotation at 0°, 20°, or 40° hip adduction in 90° hip flexion. Nine of the 12 positions were tested with maximum external rotation at positions combined with 3 hip-flexion angles (70°, 90°, and 110°) and 3 hip-adduction angles (0°, 20°, and 40°). Results: The shear elastic modulus of the PM was significantly higher in the order of 40°, 20°, and 0° of adduction and higher in external rotation than in internal rotation. The shear elastic modulus of the PM was significantly greater in combined 110° hip flexion and 40° adduction with maximum external rotation than in all other positions. Conclusion: This study revealed that the position in which the PM was most stretched was maximum external rotation with 110° hip flexion and 40° hip adduction.
Why put yourself on a pedestal? The pathogenic role of the A/E pedestal
Authors: Miner M. V. , Rauch I. 
Published: April 2024

ABSTRACT

Certain
Escherichia coli
(
E. coli
) strains are attaching and effacing (A/E) lesion pathogens that primarily infect intestinal epithelial cells. They cause actin restructuring and polymerization within the host cell to create an actin-rich protrusion below the site of adherence, termed the pedestal. Although there is clarity on the pathways initiating pedestal formation, the underlying purpose(s) of the pedestal remains ambiguous. The conservation of pedestal-forming activity across multiple pathogens and redundancy in formation pathways indicate a pathogenic advantage. However, few decisive conclusions have been drawn, given that the results vary between model systems. Some research argues that the pedestal increases the colonization capability of the bacterium. These studies utilize A/E pathogens specifically deficient in pedestal formation to evaluate adhesion and intestinal colonization following infection. There have been many proposed mechanisms for the colonization benefit conferred by the pedestal. One suggested benefit is that the pedestal allows for direct cytosolic anchoring through incorporation of the established host cortical actin, causing a stable link between the pathogen and cell structure. The pedestal may confer enhanced motility, as enteropathogenic
E. coli
(EPEC) and enterohemorrhagic
E. coli
(EHEC) are better able to migrate on the surface of host cells and infect neighboring cells in the presence of the pedestal. Additionally, some research suggests that the pedestal improves effector delivery. This review will investigate the purpose of pedestal formation using evidence from recent literature and will critically evaluate the methodology and model systems. Most importantly, we will contextualize the proposed functions to reconcile potential synergistic effects.
Novel mutation N588 residue in the NS1 protein of feline parvovirus greatly augments viral replication
Authors: Li Lisha , Liu Zirui , Liang Rui , Yang Mengfang , Yan Yuanyuan , Jiao Yuzhou , Jiao Zhe , Hu Xiaoshuai , Li Mengxia , Shen Zhou , Peng Guiqing 
Published: April 2024

ABSTRACT

Feline parvovirus (FPV) infection is highly fatal in felines. NS1, which is a key nonstructural protein of FPV, can inhibit host innate immunity and promote viral replication, which is the main reason for the severe pathogenicity of FPV. However, the mechanism by which the NS1 protein disrupts host immunity and regulates viral replication is still unclear. Here, we identified an FPV M1 strain that is regulated by the NS1 protein and has more pronounced suppression of innate immunity, resulting in robust replication. We found that the neutralization titer of the FPV M1 strain was significantly lower than that of the other strains. Moreover, FPV M1 had powerful replication ability, and the FPV M1-NS1 protein had heightened efficacy in repressing interferon-stimulated genes (ISGs) expression. Subsequently, we constructed an FPV reverse genetic system, which confirmed that the N588 residue of FPV M1-NS1 protein is a key amino acid that bolsters viral proliferation. Recombinant virus containing N588 also had stronger ability to inhibit ISGs, and lower ISGs levels promoted viral replication and reduced the neutralization titer of the positive control serum. Finally, we confirmed that the difference in viral replication was abolished in type I IFN receptor knockout cell lines. In conclusion, our results demonstrate that the N588 residue of the NS1 protein is a critical amino acid that promotes viral proliferation by increasing the inhibition of ISGs expression. These insights provide a reference for studying the relationship between parvovirus-mediated inhibition of host innate immunity and viral replication while facilitating improved FPV vaccine production.

IMPORTANCE
FPV infection is a viral infectious disease with the highest mortality rate in felines. A universal feature of parvovirus is its ability to inhibit host innate immunity, and its ability to suppress innate immunity is mainly accomplished by the NS1 protein. In the present study, FPV was used as a viral model to explore the mechanism by which the NS1 protein inhibits innate immunity and regulates viral replication. Studies have shown that the FPV-NS1 protein containing the N588 residue strongly inhibits the expression of host ISGs, thereby increasing the viral proliferation titer. In addition, the presence of the N588 residue can increase the proliferation titer of the strain 5- to 10-fold without affecting its virulence and immunogenicity. In conclusion, our findings provide new insights and guidance for studying the mechanisms by which parvoviruses suppress innate immunity and for developing high-yielding FPV vaccines.
VP2 mediates the release of the feline calicivirus RNA genome by puncturing the endosome membrane of infected cells
Authors: Sun Weiyao , Wang Ming , Shi Zhibin , Wang Pengfei , Wang Jinhui , Du Bingchen , Wang Shida , Sun Zhenzhao , Liu Zaisi , Wei Lili , Yang Decheng , He Xijun , Wang Jingfei 
Published: April 2024

ABSTRACT

Feline calicivirus (FCV) is one of the few members of the
Caliciviridae
family that grows well in cell lines and, therefore, serves as a surrogate to study the biology of other viruses in the family. Conley et al. (
14
) demonstrated that upon the receptor engagement to the capsid, FCV VP2 forms a portal-like assembly, which might provide a channel for RNA release. However, the process of calicivirus RNA release is not yet fully understood. Our findings suggest that the separation of the FCV capsid from its genome RNA (gRNA) occurs rapidly in the early endosomes of infected cells. Using a liposome model decorated with the FCV cell receptor fJAM-A, we demonstrate that FCV releases its gRNA into the liposomes by penetrating membranes under low pH conditions. Furthermore, we found that VP2, which is rich in hydrophobic residues at its N-terminus, functions as the pore-forming protein. When we substituted the VP2 N-terminal hydrophobic residues, the gRNA release efficacy of the FCV mutants decreased. In conclusion, our results suggest that in the acidic environment of early endosomes, FCV VP2 functions as the pore-forming protein to mediate gRNA release into the cytoplasm of infected cells. This provides insight into the mechanism of calicivirus genome release.

IMPORTANCE
Research on the biology and pathogenicity of certain caliciviruses, such as Norovirus and Sapovirus, is hindered by the lack of easy-to-use cell culture system. Feline calicivirus (FCV), which grows effectively in cell lines, is used as a substitute. At present, there is limited understanding of the genome release mechanism in caliciviruses. Our findings suggest that FCV uses VP2 to pierce the endosome membrane for genome release and provide new insights into the calicivirus gRNA release mechanism.
Efficacy of host cell serine protease inhibitor MM3122 against SARS-CoV-2 for treatment and prevention of COVID-19
Authors: Boon Adrianus C. M. , Bricker Traci L. , Fritch Ethan J. , Leist Sarah R. , Gully Kendra , Baric Ralph S. , Graham Rachel L. , Troan Brigid V. , Mahoney Matthew , Janetka James W. 
Published: April 2024

ABSTRACT

We developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases, including transmembrane protease serine 2 (TMPRSS2), matriptase, and hepsin. TMPRSS2 is a membrane-associated protease that is highly expressed in the upper and lower respiratory tracts and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell entry, replication, and dissemination of new virus particles. We have previously shown that compound MM3122 exhibited subnanomolar potency against all three proteases and displayed potent antiviral effects against SARS-CoV-2 in a cell viability assay. Herein, we demonstrate that MM3122 potently inhibits viral replication in human lung epithelial cells and is also effective against the EG.5.1 variant of SARS-CoV-2. Furthermore, we evaluated MM3122 in a mouse model of COVID-19 and demonstrated that MM3122 administered intraperitoneally (IP) before (prophylactic) or after (therapeutic) SARS-CoV-2 infection had significant protective effects against weight loss and lung congestion and reduced pathology. Amelioration of COVID-19 disease was associated with a reduction in proinflammatory cytokine and chemokine production after SARS-CoV-2 infection. Prophylactic, but not therapeutic, administration of MM3122 also reduced virus titers in the lungs of SARS-CoV-2-infected mice. Therefore, MM3122 is a promising lead candidate small-molecule drug for the treatment and prevention of infections caused by SARS-CoV-2 and other coronaviruses.

IMPORTANCE
SARS-CoV-2 and other emerging RNA coronaviruses are a present and future threat in causing widespread endemic and pandemic infection and disease. In this paper, we have shown that the novel host cell protease inhibitor, MM3122, blocks SARS-CoV-2 viral replication and is efficacious as both a prophylactic and a therapeutic drug for the treatment of COVID-19 given intraperitoneally in mice. Targeting host proteins and pathways in antiviral therapy is an underexplored area of research, but this approach promises to avoid drug resistance by the virus, which is common in current antiviral treatments.
The virome of the kitome: small circular virus-like genomes in laboratory reagents
Authors: Duan Jiayi , Keeler Emma , McFarland Alexander , Scott Phillip , Collman Ronald G. , Bushman Frederic D. 
Published: April 2024

ABSTRACT

In the course of studying the virome of protozoan parasites, we identified small circular genomes resembling viruses, which turned out to be contaminants from an RNA purification kit. We report their sequences here so others can detect possible contamination in their samples by aligning them to these targets.
Progressive development of stylolites in cryptocrystalline quartz
Authors: Hou Zhaoliang , Qiu Kun-Feng , Rogowitz Anna , Schultz Richard A. , Yu Hao-Cheng , Grasemann Bernhard 
Published: April 2024

Abstract
Stylolites are common dissolution structures in carbonate rocks in the upper crust and document a coupled physical-chemical feedback during pressure solution in rocks. By applying high-resolution electron-based analysis we investigate a rare example of stylolites in cryptocrystalline quartz (novaculite) from western Sichuan Basin, China. The investigated stylolites exhibit an increased amplitude from the tip toward the center, which correlates with the maturity of stylolites and thus provides an excellent opportunity to infer the dynamic processes operating during stylolite formation. Microstructurally, stylolites are characterized by a concentration of biotite and hematite, dissolving irregular quartz grains, and the occurrence of dissolution porosity. By investigating the progressive co-variations between stylolite amplitude and microstructure characteristics from the stylolite tip toward the center, we demonstrate, for the first time, the evidence of stylolite growth through anticracks. It is inferred that stylolites in cryptocrystalline quartz originate from the propagation of mode I micro-cracks around pre-existing biotite, followed by pore-scale dissolution. Both processes, micro-cracking and dissolution, are interacting and co-evolving via a self-organization fashion during shortening. Our study contributes to the ongoing debate about whether stylolites are conduits or barriers for fluid flow.