bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relationship of Vaccine Uptake and COVID-19 Infections Among Nursing Home Staff and Residents in Missouri: A Measure of Risk by Community Mobility
Authors: Scroggins Stephen , Little Germysha , Okala Odiraa , Ellis Matthew , Shacham Enbal 
Published: October 2023

Background:
As the COVID-19 pandemic progressed across the United States, older adults living in nursing home (NH) facilities were disproportionately affected because of living in communal spaces with close proximity to others, age-related medical conditions, and constant contact with staff who may support multiple clients and facilities. While these populations are particularly at risk, there has been limited research focused on the management of the potential vectors of COVID-19 infection.

Methods:
Data from the Centers for Medicare & Medicaid Services (CMS) COVID-19 reporting system assessing weekly observations of COVID-19 case counts among NH residents and COVID-19 vaccination rates among NH staff and residents in the states of Missouri and Illinois (n = 877) from May 24, 2021, to August 28, 2021, were used. This ecological study, using results from the CMS COVID-19 reporting system, local COVID-19 rates, and NH-level demographic characteristics, conducted a zero inflation mode to determine the association between NH staff vaccine uptake and COVID-19 cases among NH residents.

Results:
Among the total 11 195 weekly observations within the NH facilities, zero cases of COVID-19 were reported during 10 683 (95%) of those weeks, supporting the use of a zero-inflated model. Results show that staff vaccination rates were significantly associated with a decrease in COVID-19 mortality. This study identified that for every percentage increase in staff vaccine coverage, the rate of COVID-19 among residents decreased by 2%.

Discussion:
These findings suggest that NH staff vaccination rates are significantly associated with the rate of COVID-19 outbreaks among NH residents. Community median income was associated with an increased likelihood of infection. Future research that explores associations with employment benefits and staff mobility, particularly in vulnerable populations, should be implemented in future vaccination strategic planning.
Comparing Cancer Incidence in an Observational Cohort of Medicaid Beneficiaries With and Without HIV, 2001–2015
Authors: Rudolph Jacqueline E. , Calkins Keri L. , Xu Xiaoqiang , Wentz Eryka , Pirsl Filip , Visvanathan Kala , Lau Bryan , Joshu Corinne E. 
Published: October 2023

Background:
Life expectancy among people with HIV (PWH) is increasing, making chronic conditions—including cancer—increasingly relevant. Among PWH, cancer burden has shifted from AIDS-defining cancers (ADCs) toward non–AIDS-defining cancers (NADCs).

Setting:
We described incidence of cancer in a claims-based cohort of Medicaid beneficiaries. We included 43,426,043 Medicaid beneficiaries (180,058 with HIV) from 14 US states, aged 18–64, with >6 months of enrollment (with no dual enrollment in another insurance) and no evidence of a prveious cancer.

Methods:
We estimated cumulative incidence of site-specific cancers, NADCs, and ADCs, by baseline HIV status, using age as the time scale and accounting for death as a competing risk. We compared cumulative incidence across HIV status to estimate risk differences. We examined cancer incidence overall and by sex, race/ethnicity, and calendar period.

Results:
PWH had a higher incidence of ADCs, infection-related NADCs, and death. For NADCs such as breast, prostate, and colon cancer, incidence was similar or higher among PWH below age 50, but higher among those without HIV by age 65. Incidence of lung and head and neck cancer was always higher for female beneficiaries with HIV, whereas the curves crossed for male beneficiaries. We saw only small differences in incidence trends by race/ethnicity.

Conclusion:
Our findings suggest an increased risk of certain NADCs at younger ages among PWH, even when compared against other Medicaid beneficiaries, and highlight the importance of monitoring PWH for ADCs and NADCs. Future work should explore possible mechanisms explaining the differences in incidence for specific cancer types.
Respiratory syncytial virus in children: epidemiology and clinical impact post-COVID-19
Authors: Rice Emily , Oakes Daniel B. , Holland Charlie , Moore Hannah C. , Blyth Christopher C. 
Published: October 2023

Purpose of review
Respiratory syncytial virus (RSV) remains a leading cause of mortality and morbidity worldwide. RSV seasonality was disrupted by COVID-19-associated nonpharmaceutical interventions (NPIs). We review RSV seasonality, molecular epidemiology, clinical manifestations, and community awareness to inform future prevention strategies.

Recent findings
An initial reduction of RSV disease observed with NPIs, and subsequent global resurgence was associated with a collapse in genetic diversity. A lack of immunity is suggested to have contributed to the resurgence of RSV cases experienced post COVID-19. The median age of children admitted with RSV increased during the resurgence, likely secondary to the expanded cohort of RSV-immune naive children. The pandemic also played a role in increased community awareness, which can be utilized as part of a coordinated public health effort to introduce prevention strategies. Further education on signs and symptoms of RSV is still required.

Summary
mAbs and maternal vaccines targeting RSV have the potential to reduce paediatric morbidity, however this new era of RSV prevention will require ongoing research to facilitate community awareness and engagement, and better respiratory surveillance. Tackling the global burden of RSV will require a coordinated effort and measures to ensure access and affordability of new prevention strategies.
Nipple-Sparing Mastectomy With Immediate Reconstruction After Breast-Conserving Therapy and Radiation
Authors: King Caroline A. , Bartholomew Alex J. , Dabic Stefan , Sogunro Olutayo , Perez-Alvarez Idanis M. , Welschmeyer Alexandra F. , Sosin Michael , Thibodeau Renee M. , Fan Kenneth L. , Song David H. , Greenwalt Ian T. , Tousimis Eleni A. 
Published: October 2023

Introduction
Nipple-sparing mastectomy (NSM) offers improved, patient-centered outcomes with demonstrated oncologic safety (Ann Surg Oncol 2020;27:344–351). Indications for NSM continue to expand to patients outside of the traditional eligibility criteria, including those with prior breast-conserving therapy (BCT) with radiotherapy. Currently, limited data exist evaluating both short- and long-term outcomes in patients proceeding to NSM after prior BCT.

Methods
All patients undergoing bilateral NSM in a single institution from 2002 through 2017 with history of prior BCT were included in the final cohort, without exclusions. A retrospective chart review was performed to identify patient demographics, operative details, and complications. Outcomes assessed included early complications (<30 days from NSM), late complications (>30 days), rates of prosthetic failure, unplanned reoperations, and reconstructive failures, as well as oncologic safety. Student t, χ2, and Fisher exact tests were used to analyze outcomes of paired (BCT vs non-BCT) breasts within each patient.

Results
A total of 17 patients undergoing 34 NSMs were included. Each had a history of BCT and either ipsilateral breast recurrence (64.7%), risk-reducing NSM (23.5%), or a new contralateral primary cancer (11.8%). The cohort had a mean age of 51.1 years. With regard to acute complications (ischemia, infection, nipple-areolar complex or flap ischemia or necrosis, and wound dehiscence), there was no significant difference noted between breasts with prior BCT versus no prior BCT overall (41.2% vs 35.3%, respectively; P = 0.724). Complications occurring after 30 days postoperatively (capsular contracture, contour abnormality, animation deformity, bottoming out, rotation, and rippling) in prior BCT breasts versus no prior BCT had no significant differences overall (58.8% vs 41.2% respectively; P = 0.303). The mean follow-up was 5.5 years, during which no patients had a reported locoregional or distant recurrence in either breast.

Conclusions
No significant differences in early or late complications were identified between breasts in patients undergoing bilateral NSM with a history of unilateral BCT and XRT. In the 5.5 years of follow-up, there were no recurrences, lending support to NSM for management of recurrent disease in addition to National Comprehensive Cancer Network–recommended total mastectomy. We propose that NSM should not be contraindicated in patients exposed to radiation with BCT.
TRAUMA-INDUCED COAGULOPATHY: WHAT YOU NEED TO KNOW
Authors: Buzzard Lydia , Schreiber Martin 
Published: October 2023

SUMMARY
Trauma-induced coagulopathy (TIC) is a global inflammatory state accompanied by coagulation derangements, acidemia, and hypothermia, that occurs after traumatic injury. It occurs in approximately 25% of severely-injured patients, and its incidence is directly related to injury severity. The mechanism of TIC is multi-faceted; proposed contributing factors include dysregulation of activated protein C, increased tPA, systemic endothelial activation, decreased fibrinogen, clotting factor consumption, and platelet dysfunction. Effects of TIC include systemic inflammation, coagulation derangements, acidemia, and hypothermia. TIC may be diagnosed by conventional coagulation tests including platelet count, Clauss assay, INR, thrombin time, PT, and aPTT; viscoelastic hemostatic assays such as thrombelastography (TEG) and rotational thrombelastography (ROTEM), or by a clinical scoring system known as the Trauma Induced Coagulopathy Clinical Score (TICCS). Preventing TIC begins in the prehospital phase with early hemorrhage control, blood product resuscitation, and TXA therapy. Early administration of prothrombin complex concentrate (PCC) is also being studied in the prehospital environment. The mainstays of TIC treatment include hemorrhage control, blood and component transfusions, and correction of abnormalities such as hypocalcemia, acidosis, and hypothermia.
The embryonic role of juvenile hormone in the firebrat,Thermobia domestica,reveals its function before its involvement in metamorphosis
Authors: Truman James W. , Riddiford Lynn M. , Konopová Barbora , Nouzova Marcela , Noriega Fernando G. , Herko Michelle 
Published: October 2023

ABSTRACTTo gain insights into how juvenile hormone (JH) came to regulate insect metamorphosis, we studied its function in the ametabolous firebrat,Thermobia domestica. Highest levels of JH occur during late embryogenesis, with only low levels thereafter. Loss-of-function and gain-of-function experiments show that JH acts on embryonic tissues to suppress morphogenesis and cell determination and to promote their terminal differentiation. Similar embryonic actions of JH on hemimetabolous insects with short germ band embryos indicate that JH’s embryonic role preceded its derived function as the postembryonic regulator of metamorphosis. The postembryonic expansion of JH function likely followed the evolution of flight. Archaic flying insects were considered to lack metamorphosis because tiny, movable wings were evident on the thoraces of young juveniles and their positive allometric growth eventually allowed them to support flight in late juveniles. Like inThermobia, we assume that these juveniles lacked JH. However, a postembryonic reappearance of JH during wing morphogenesis in the young juvenile likely redirected wing development to make a wing pad rather than a wing. Maintenance of JH then allowed wing pad growth and its disappearance in the mature juvenile then allowed wing differentiation. Subsequent modification of JH action for hemi- and holometabolous lifestyles are discussed.SignificanceThe likely action of this sesquiterpene hormone as a morphogenesis-to-differentiation switch in archaic embryos preadapted it for later assuming its function as thestatus quoregulator of insect metamorphosis.
Woollymutation withGet02locus overcomes the polygenic nature of trichome-based pest resistance in tomato
Authors: Vendemiatti Eloisa , Hernández-De Lira Inty O. , Snijders Roxane , Torne Tanmayee , Therezan Rodrigo , Prants Gabriela , Lopez-Ortiz Carlos , Reddy Umesh , Bleeker Petra , Schenck Craig A. , Peres Lázaro Eustáquio Pereira , Benedito Vagner Augusto 
Published: October 2023

ABSTRACTType-IV glandular trichomes, which only occur in the juvenile phase of tomato development, produce acylsugars (AS) that broadly protect against arthropod herbivory. Previously, we introgressed the capacity to retain type-IV trichomes in the adult phase fromSolanum galapagenseinto the cv. Micro-Tom (MT). The resulting MT-Getline contained five loci associated with enhancing the density of type-IV trichomes in adult plants. We genetically dissected MT-Getand obtained a sub-line containing only the locus on chromosome 2 (MT-Get02). This genotype displayed about half the density of type-IV trichomes compared to the wild progenitor. However, when we stacked the gain-of-function allele ofWOOLLY, which codes for a HD-ZIP IV transcription factor, MT-Get02/Woexhibited double the number of type-IV trichomes compared toS. galapagense. This discovery corroborates previous reports positioningWOOLLYas a master regulator of trichome development. AS levels in MT-Get02/Wowere comparable to the wild progenitor, although the composition of AS types differed, especially regarding less AS with medium-length acyl chains. Agronomical parameters of MT-Get02/Wo, including yield, were comparable to MT. Pest resistance assays showed enhanced protection against whitefly, caterpillar, and the fungusSeptoria lycopersici. However, resistance levels did not reach that of the wild progenitor, suggesting the specificity of particulars AS types in the pest resistance mechanism. Our findings in trichome-mediated resistance advance the development of robust, naturally resistant tomato varieties, harnessing the potential of natural genetic variation. Moreover, by manipulating only two loci, we achieved exceptional results for a highly complex, polygenic trait, such as herbivory resistance in tomato.
Accelerated brain change in healthy adults is associated with genetic risk for Alzheimer’s disease and uncovers adult lifespan memory decline
Authors: Roe James M. , Vidal-Piñeiro Didac , Sørensen Øystein , Grydeland Håkon , Leonardsen Esten H. , Iakunchykova Olena , Pan Mengyu , Mowinckel Athanasia , Strømstad Marie , Nawijn Laura , Milaneschi Yuri , Andersson Micael , Pudas Sara , Bråthen Anne Cecilie Sjøli , Kransberg Jonas , Falch Emilie Sogn , Øverbye Knut , Kievit Rogier A. , Ebmeier Klaus P. , Lindenberger Ulman , Ghisletta Paolo , Demnitz Naiara , Boraxbekk Carl-Johan ,   the Alzheimer‘s Disease Neuroimaging Initiative,   the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing, Penninx Brenda , Bertram Lars , Nyberg Lars , Walhovd Kristine B. , Fjell Anders M. , Wang Yunpeng 
Published: October 2023

AbstractAcross healthy adult life our brains undergo gradual structural change in a pattern of atrophy that resembles accelerated brain changes in Alzheimer’s disease (AD). Here, using four polygenic risk scores for AD (PRS-AD) in a longitudinal adult lifespan sample aged 30 to 89 years (2-7 timepoints), we show that healthy individuals who lose brain volume faster than expected for their age, have a higher genetic AD risk. We first demonstrate PRS-AD associations with change in early Braak regions, namely hippocampus, entorhinal cortex, and amygdala, and find evidence these extend beyond that predicted byAPOEgenotype. Next, following the hypothesis that brain changes in ageing and AD are largely shared, we performed machine learning classification on brain change trajectories conditional on age in longitudinal AD patient-control data, to obtain a list of AD-accelerated features and model change in these in adult lifespan data. We found PRS-AD was associated with a multivariate marker of accelerated change in many of these features in healthy adults, and that most individuals above ∼50 years of age are on an accelerated change trajectory in AD-accelerated brain regions. Finally, high PRS-AD individuals also high on a multivariate marker of change showed more adult lifespan memory decline, compared to high PRS-AD individuals with less brain change. Our results support a dimensional account linking normal brain ageing with AD, suggesting AD risk genes speed up the shared pattern of ageing- and AD-related neurodegeneration that starts early, occurs along a continuum, and tracks memory change in healthy adults.
Comparison of germline and somatic structural variants in cancers reveal systematic differences in variant generating and selection processes
Authors: Chukwu Wolu , Lee Siyun , Crane Alexander , Zhang Shu , Webster Sophie , Mittra Ipsa , Imielinski Marcin , Beroukhim Rameen , Dubois Frank , Dalin Simona 
Published: October 2023

AbstractAlthough several recent studies have characterized structural variants (SVs) in germline and cancer genomes, the features of SVs in these different contexts have not been directly compared. We examined similarities and differences between 2 million germline and 115 thousand tumor SVs from a cohort of 963 patients from The Cancer Genome Atlas (TCGA). We found significant differences in features related to their genomic sequences and localization that suggest differences between SV-generating processes and selective pressures. For example, we found that transposon-mediated processes shape germline much more than somatic SVs, while somatic SVs more frequently show features characteristic of chromoanagenesis. These differences were extensive enough to enable us to develop a classifier-“the great GaTSV”-that accurately distinguishes between germline and cancer SVs in tumor samples that lack a matched normal sample.
Mutations in geneslpxL1, bamAandpmrBimpair the susceptibility of cystic fibrosis strains ofPseudomonas aeruginosato murepavadin
Authors: Ghassani Aya , Triponney Pauline , Bour Maxime , Plesiat Patrick , Jeannot Katy ,   MucoMicrobes study Group
Published: October 2023

AbstractMurepavadin is a peptidomimetic exhibiting specific inhibitory activity againstPseudomonasspecies. In the present study, itsin vitroactivity was assessed on 230 cystic fibrosis (CF) strains ofP. aeruginosaisolated from twelve French hospitals, in comparison with twelve other antipseudomonal antibiotics. Although murepavadin is still in pre-clinical stage of development, 9.1% (n=21) of the strains displayed a resistance superior to 4 mg/L, a level at least 128-fold higher than the modal MIC value of the whole collection (≤ 0.06 mg/L). Whole-genome sequencing of these 21 strains along with more susceptible isogenic counterparts coexisting in the same patients revealed diverse mutations in genes involved in the synthesis (lpxL1andlpxL2) or transport of lipopolysaccharides (bamA, lptD, andmsbA), or encoding histidine kinases of two-component systems (pmrBandcbrA). Allelic replacement experiments with wild-type reference strain PAO1 confirmed that alteration of geneslpxL1, bamAand/orpmrBcan increase murepavadin resistance from 8- to 32-fold. Furthermore, we found that specific amino-acid substitutions in histidine kinase PmrB (G188D, Q105P, and D45E) reduce the susceptibility ofP. aeruginosato murepavadin, colistin and tobramycin, three antibiotics used or intended to be used (murepavadin) in aerosols to treat colonized CF patients. Whether colistin or tobramycin may select mutants resistant to murepavadin or the opposite needs to be addressed by clinical studies.
25-hydroxycholesterol mediates brain cytokine production and neutrophil infiltration in a mouse model of lipopolysaccharide-induced neuroinflammation
Authors: Romero Johnathan , Toral-Rios Danira , Yu Jinsheng , Paul Steven M , Cashikar Anil G 
Published: October 2023

ABSTRACTNeuroinflammation has been implicated in the pathogenesis of several neurologic and psychiatric disorders. Microglia are key drivers of neuroinflammation and in response to different inflammatory stimuli overexpress a proinflammatory signature of genes. Among these,Ch25his a gene overexpressed in brain tissue from Alzheimer’s disease as well as various mouse models of neuroinflammation.Ch25hencodes cholesterol 25-hydroxylase, an enzyme that hydroxylates cholesterol to form 25-hydroxycholesterol (25HC). 25HC, an immune-oxysterol primarily produced by activated microglia, is further metabolized to 7α,25-dihydroxycholesterol, which is a potent chemoattractant for leukocytes. We have also previously shown that 25HC increases production and secretion of the proinflammatory cytokine, IL-1β, by mouse microglia treated with lipopolysaccharide (LPS). In the present study, wildtype (WT) andCh25h-knockout (CKO) mice were peripherally administered LPS to induce an inflammatory state in the brain. In LPS-treatedWTmice,Ch25hexpression and 25HC levels increased in brain relative to vehicle-treatedWTmice. Interestingly, 25HC levels were significantly higher in LPS-treatedWTfemale compared to male mice. Activation of microglia and astrocytes in response to systemic LPS was suppressed inCKOmice relative toWTmice. Proinflammatory cytokine production and intra-parenchymal infiltration of neutrophils strongly correlated with brain 25HC levels and were significantly lower inCKOcompared toWTmice. Overall, our results show that 25HC mediates a sex-specific proinflammatory response in the brain characterized by activation of both microglia and astrocytes but also by neutrophil migration into the brain parenchyma presumably due to 7α,25-diHC produced from 25HC.
Sexually dimorphic effects of pexidartinib on nerve injury-induced neuropathic pain in mice
Authors: Saika Fumihiro , Fukazawa Yohji , Hatano Yu , Kishioka Shiroh , Hino Shinjiro , Suzuki Kentaro , Kiguchi Norikazu 
Published: October 2023

AbstractBackgroundIt is well-established that spinal microglia and peripheral macrophages play critical roles in the etiology of neuropathic pain; however, growing evidence suggests sex differences in pain hypersensitivity owing to microglia and macrophages. Therefore, it is crucial to understand sex- and androgen-dependent characteristics of pain-related myeloid cells in mice with nerve injury-induced neuropathic pain.MethodsThe current study was performed using normal male and female mice, as well as gonadectomized (GDX) male mice. To deplete microglia and macrophages, pexidartinib (PLX3397), an inhibitor of the colony-stimulating factor 1 receptor, was orally administered, and mice were subjected to partial sciatic nerve ligation (PSL). Immunohistochemistry was performed to visualize microglia and macrophages, and PSL-induced mechanical allodynia was evaluated using the von Frey test.ResultsFollowing PSL induction, healthy male and female mice and male GDX mice exhibited similar levels of spinal microglial activation, peripheral macrophage accumulation, and mechanical allodynia. Treatment with PLX3397 significantly suppressed mechanical allodynia in normal males; this was not observed in female and GDX male mice. Sex- and androgen-dependent differences in the PLX3397-mediated preventive effects were observed on spinal microglia and dorsal root ganglia (DRG) macrophages, as well as in expression patterns of pain-related inflammatory mediators in these cells. Conversely, no sex- or androgen-dependent differences were detected in sciatic nerve macrophages, and inhibition of peripheral CC-chemokine receptor 5 prevented neuropathic pain in both sexes.ConclusionCollectively, these findings demonstrate the presence of considerable sex- and androgen-dependent differences in the etiology of neuropathic pain in spinal microglia and DRG macrophages but not in sciatic nerve macrophages. Given that the mechanisms of neuropathic pain may differ among experimental models and clinical conditions, accumulating several lines of evidence is crucial to comprehensively clarifying the sex-dependent regulatory mechanisms of pain.