bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Integration and Application of the 2022 WHO Pituitary Tumor Classification
Authors: Asa Sylvia L , Ezzat Shereen , Mete Ozgur
Published: January 2025

The pituitary is a complex endocrine organ that gives rise to adenohypophysial epithelial neuroendocrine tumors, to hypothalamic neuroendocrine neuronal neoplasms, to non-endocrine glial-related pituicytomas and to Rathke’s pouch-derived craniopharyngiomas and pituitary blastomas. The past 30 years have seen significant advances in the classification of these tumors based on cell lineages, molecular alterations and biomarker features that distinguish tumor types and their subtypes. Adenohypophysial cells give rise to pituitary neuroendocrine tumors (PitNETs) that usually follow one of three cell differentiation pathways. Pituicytomas have multiple morphologic variants and hypothalamic neuronal tumors can be gangliocytomas composed of magnocellular neurons or neurocytomas composed of small neurocytes. Craniopharyngiomas have two distinct families, papillary and adamantinomatous, with different alterations in signaling pathways. Pituitary blastomas are primitive tumors composed of an admixture of immature elements of Rathke’s pouch with immature but differentiated hormone-secreting adenohypophysial cells. These various tumors are associated with specific clinical manifestations, creating a complex clinico-radiologic-pathologic classification that has both important clinical distinctions but also predictive therapeutic value. Syndromic disease has allowed the identification of genes that may be implicated in the development of these tumors, but the majority are sporadic tumors that, with a few exceptions, have no recurrent genetic alterations. The structure-function correlations that have been elucidated are critical to allow subclassification of clinical disorders that will pave the way for further advances in understanding genetic predisposition and environmental factors that alter epigenetic profiles of pituitary cells.
Circulating PD-1hi CXCR5– and CXCR5+ CD4 T cells are elevated in patients with newly diagnosed giant cell arteritis, and predict relapse
Authors: Monjo-Henry Irene , Nieto-Carvalhal Beatriz , Uyaguari Mariela , García-Carazo Sara , Balsa Alejandro , de Miguel Eugenio , Miranda-Carús María-Eugenia
Published: January 2025

Objectives

GCA is a large/medium-vessel granulomatous vasculitis, and the Programmed Cell Death 1/Programmed Cell Death-ligand-1 (PD-1/PD-L1) coinhibitory pathway seems to be implicated in its pathogenesis. CD4 T cells expressing high PD-1 levels, CD4+CXCR5–PD-1hi peripheral helper (Tph) and CD4+CXCR5+PD-1hi follicular helper T cells (Tfh) are key mediators of autoimmunity. Their frequencies are elevated in the peripheral blood of subjects with several autoimmune conditions but have not been investigated in GCA. Our objective was to study the frequency of circulating Tph (cTph) and Tfh (cTfh) in patients with newly diagnosed GCA (nGCA).

Methods

Prospective, non-interventional study on consecutive patients referred to our US GCA fast-track clinic over a period of 24 months. Peripheral blood was drawn immediately upon initial diagnosis. For each patient, an age- and gender-matched healthy control (HC) was included. Peripheral blood mononuclear cells isolated by Ficoll-Hypaque were examined by cytometry. Patients were subsequently treated with standard therapy according to the updated 2018 EULAR recommendations.

Results

Sixty-five nGCA patients were included. As compared with HC, nGCA patients presented at baseline with an increased frequency of cTph and cTfh cells. Among the 46 patients who could be followed up for 12 months, 19 experienced a relapse. The baseline frequency of cTph and cTfh cells had been significantly lower in patients who relapsed as compared with those who did not. A cTph cell frequency <1.0 predicted relapse with a sensitivity of 90% and specificity of 93%.

Conclusion

nGCA patients demonstrate increased baseline cTph and cTfh cell frequencies. Lower baseline proportions of cTph and cTfh cells associate with relapse.
Toxic epidermal necrolysis induced by axitinib in a patient with advanced lung adenocarcinoma
Authors: Wang Na , Li Dongkai , He Huaiwu , Long Yun , Liu Dawei
Published: January 2025

Patients taking oral EGFR inhibitors should be alert to the risk of TEN if they suddenly develop widespread rash.
Phellodendrine inhibits oxidative stress and promotes autophagy by regulating the AMPK/mTOR pathway in burn sepsis-induced intestinal injury
Authors: Ding Wei , Qian Kun , Bao Wenxiu , Wang Zhen
Published: January 2025

Intestinal injury is an important complication of burn sepsis with limited therapeutic choices. Phellodendrine is a promising compound for gastrointestinal inflammatory diseases and is extracted from the traditional Chinese medicine phellodendron bark. The study aimed to explore the role of phellodendrine against oxidative stress and autophagy in burn sepsis-induced intestinal injury. A mouse model of burn sepsis model was established by intraperitoneally injecting 10 mg/kg lipopolysaccharide (LPS) to mice burned by boiled water. Phellodendrine (30 mg/kg) was injected into mice in the drug group after scalding and before LPS injection. Hematoxylin and eosin staining was performed to observe histopathological changes in murine small intestines. TdT-mediated dUTP Nick-End Labeling (TUNEL) assay was performed to evaluate intestinal cell apoptosis. Immunofluorescence staining was performed to measure the expression and distribution of autophagy markers, light chain 3II (LC3II) and p62 in intestinal tissues. Oxidative stress indicators were detected using corresponding commercial kits. Protein levels of apoptotic markers, autophagy markers, and factors involved in adenosine monophosphate-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) pathway in intestines were quantified by western blotting. Phellodendrine attenuated bun sepsis-induced intestinal pathological changes. Meanwhile, aggravated cell apoptosis, reduction of antioxidant enzymes, and downregulation of autophagy markers in intestinal tissues of burn sepsis group were all improved by phellodendrine. In addition, phellodendrine activated the phosphorylation (p) of AMPK and inhibited p-mTOR signaling in intestines of burn septic mice. In conclusion, phellodendrine suppresses oxidative stress and activates autophagy in burn sepsis-induced intestinal injury by activating AMPK and inhibiting mTOR signaling.
Driver injury severity analysis of work zone crashes: A Bayesian hierarchical generalized ordered probit approach
Authors: Huang Peng , Xiong Yanwen , Tang Shijiang , Wang Shaohua , Zeng Qiang , Lee Jaeyoung Jay
Published: January 2025

Highway work zones are locations where severe traffic crashes tend to occur. Most of the extant research on work zone crash severity neglects the discrepancy in the injuries sustained by different drivers involved in the same crash. Admittedly, it is essential to analyze crash-level factors to their highest injury severity; but it is equally important to understand driver-level contributing factors to their injury severity to establish effective safety countermeasures to minimize drivers’ injury severity. Thus, this research aims to identify the factors with significant impacts on driver injury severity of work zone crashes and estimate their effects on each severity level. Data of 3,880 drivers involved in 2,134 work zone crashes are obtained from the Crash Report Sampling System (CRSS) database of the United States and employed for the empirical investigation. A Bayesian hierarchical generalized ordered probit model is advocated for analyzing the driver injury severity. Model performance indices suggest that the advocated hierarchical model is superior to the generalized ordered probit model, and considerable within-crash correlation is found across the observed driver injury severity. The estimated parameters show that driver age and gender, alcohol use, vehicle age and type, speeding and speed limit, weather condition, lighting condition, and crash type have significant effects on the driver injury severity in work zone crashes. Marginal effects of the significant factors on each divided injury severity level are also estimated. Countermeasures are proposed from the results to reduce severe injuries sustained by drivers involved in work zone crashes.
Will the real invasive snail please stand up? A phylogenetic reconsideration of Paralaoma servilis (Shuttleworth, 1852) (Gastropoda: Stylommatophora: Punctidae)
Authors: Nekola Jeffrey C , Brook Fred J , Foon Junn Kitt , Horsáková Veronika , Ishii Yasuto , Köhler Frank , Líznarová Eva , Nováková Markéta , Saito Takumi , Salvador Rodrigo B , Horsák Michal
Published: January 2025

We reconsider the biodiversity and biogeography of Paralaoma servilis—believed to be one of the most globally invasive exotic land snails—through integrative empirical revision. Phylogenies obtained from nDNA (ELAV, ddRAD genomics) and mtDNA (COI) demonstrate that the current classification is in error, with there being at least five distinct species within P. servilis s.l. The P. servilis group as interpreted here thus includes: P. servilis, inferred to be native to south-western Pacific Rim with an adventive distribution minimally spanning North America, Europe, and the Macaronesian islands of the eastern Atlantic Ocean; P. amblygona (Reinhardt, 1877), native to Honshu, Japan; P. borealis (Pilsbry and Y. Hirase, 1905), native to Hokkaido, Japan along the Pacific Rim to the SW North American mountains; P. caputspinulae (Reeve, 1852), native to New Zealand and Lord Howe Island; and P. morti (J.C. Cox, 1864), native to south-eastern Australia. Within P. servilis, invasiveness appears limited to a single clade that may have arisen along the California coast. The work presented here is a reminder that taxonomic concepts that have not been subjected to empirical vetting can generate poor biodiversity perspectives and non-optimal conservation strategies when native species are treated as exotics.
Genome-Wide Analysis of Moniliophthora roreri Facilitates the Development of Species-Specific Primers for Biomonitoring Frosty Pod Rot of Cacao
Authors: Reis Sara Pereira Menezes , Diorato Vanessa Santana , dos Santos Júnior Almiro Neves , Barbosa Ceslaine Santos , Ciampi-Guillardi Maisa , de Andrade Edson Mario , Solis Karina Zoila , Manco Maria Julia Silva , França Franciely Santos , Vera Danilo , Catota Arturo Ivan Garzón , Niella Givaldo Rocha , Arévalo-Gardini Enrique , Bonilla José Luis Solís , Micheli Fabienne , Wong Julio Alfonso Chia , Gramacho Karina Peres
Published: January 2025

Detecting pathogens in asymptomatic plants allows for a rapid response to emerging threats, such as the introduction of new pathogens or the emergence of new resistant strains. Frosty pod rot ( Moniliophthora roreri) significantly jeopardizes cacao production by impairing pod quality and yield. However, early diagnosis is challenging due to its prolonged incubation period, compounded by symptoms resembling those of M. perniciosa, the causative agent of witches’ broom disease. To address this, a specific and sensitive quantitative real-time PCR (qPCR) assay was developed for M. roreri detection. This involved testing diagnostic primers against a panel of 252 DNA samples collected from target and nontarget species of over 13 fungal species commonly found in cacao plantations from various regions. Species-specific primer pairs were obtained through genomic comparison of Moniliophthora spp. genomes. Two primer sets, Mr77F/R and Mr78F/R, were validated using a set of M. roreri DNA samples representative of different genetic groups (Ecuador, Peru, and Mexico) and M. perniciosa, from which no amplification was detected. The limit of detection (LOD) was determined to be 0.9 ng/µl for both primers Mr77F/R and Mr78F/R. Using this set of primers, the amplification of M. roreri DNA from naturally diseased cocoa pods at various stages of infection was also successful. At the practical level, the data provided here confirm the value of molecular diagnostic testing for the early detection of M. roreri. These features are desirable for improving fungal diagnostic capacity and assisting in devising strategies to avoid pathogen dispersion within cacao-growing regions.

[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 .
Fezolinetant and Elinzanetant Therapy for Menopausal Women Experiencing Vasomotor Symptoms
Authors: Menegaz de Almeida Artur , Oliveira Paloma , Lopes Lucca , Leite Marianna , Morbach Victória , Alves Kelly Francinny , Barros Ítalo , Aquino de Moraes Francisco Cezar , Prevedello Alexandra
Published: January 2025

OBJECTIVE:

To assess the efficacy and safety of fezolinetant and elinzanetant for vasomotor symptoms in menopausal women.

DATA SOURCES:

MEDLINE, EMBASE, and Cochrane databases were systematically searched until August 22, 2024. Because the Cochrane Library included all the identified randomized controlled trials (RCTs), it was unnecessary to search ClinicalTrials.gov. The following words made up the search strategy, which was applied to the three databases: fezolinetant, elinzanetant, vasomotor symptoms, and menopause.

METHODS OF STUDY SELECTION:

Only RCTs comparing fezolinetant and elinzanetant with placebo for vasomotor symptoms in menopausal women were included.

TABULATION, INTEGRATION, AND RESULTS:

We extracted the number of patients, mean age, body mass index (BMI), and number of patients who underwent oophorectomy. Data were examined with the Mantel–Haenszel method and 95% CIs. Heterogeneity was assessed with I
2 statistics. R 4.3.2 was used for statistical analysis. Seven RCTs with 4,087 patients were included in the analysis. Fezolinetant and elinzanetant were associated with diminished vasomotor symptom frequency: fezolinetant 30 mg (mean difference 2.16, 95% CI, 1.54–2.79, I
2=0%), fezolinetant 45 mg (mean difference 2.54, 95% CI, 1.86–3.21, I
2=0%), and elinzanetant 120 mg (mean difference 2.99, 95% CI, 1.74–4.23, I
2=0%). Both drugs also showed a decrease in vasomotor symptom severity: fezolinetant 30 mg (mean difference 0.20, 95% CI, 0.09–0.33, I
2=0%), fezolinetant 45 mg (mean difference 0.24, 95% CI, 0.13–0.34, I
2=0%), and elinzanetant 120 mg (mean difference 0.36, 95% CI, 0.26–0.46, I
2=0%). Elinzanetant 120 mg showed a significant improvement in sleep quality (mean difference 4.65, 95% CI, 3.73–5.56, I
2=0%). Elinzanetant 120 mg was associated with the occurrence of drug-related adverse events (11.70% vs 20.75%, risk ratio [RR] 0.57, 95% CI, 0.39–0.82, I
2=19%) and headache (2.54% vs 8.0%, RR 0.32, 95% CI, 0.16–0.64, I
2=0%).

CONCLUSION:

In this meta-analysis, consistent results suggest that fezolinetant and elinzanetant are associated with beneficial outcomes in menopausal women with vasomotor symptoms. Elinzanetant provided a larger effect size in vasomotor symptom frequency and severity reduction and greatly improved sleep quality compared with fezolinetant.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42023469952.
Efficacy, Safety, and Immunogenicity of the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Respiratory Syncytial Virus Prefusion F Protein Vaccine Trial
Authors: Simões Eric A. F. , Pahud Barbara A. , Madhi Shabir A. , Kampmann Beate , Shittu Emma , Radley David , Llapur Conrado , Baker Jeffrey , Pérez Marc Gonzalo , Barnabas Shaun L. , Fausett Merlin , Adam Tyler , Perreras Nicole , Van Houten Marlies A. , Kantele Anu , Huang Li-Min , Bont Louis J. , Otsuki Takeo , Vargas Sergio L. , Gullam Joanna , Tapiero Bruce , Stein Renato T. , Polack Fernando P. , Zar Heather J. , Staerke Nina B. , Padilla María Duron , Richmond Peter C. , Sarwar Uzma N. , Baber James , Koury Kenneth , Lino Maria Maddalena , Kalinina Elena V. , Li Weiqiang , Cooper David , Anderson Annaliesa S. , Swanson Kena A. , Gurtman Alejandra , Munjal Iona
Published: January 2025

OBJECTIVE:

To evaluate descriptive efficacy data, exploratory immunogenicity data, and safety follow-up through study completion from the global, phase 3 MATISSE (Maternal Immunization Study for Safety and Efficacy) maternal vaccination trial of bivalent respiratory syncytial virus (RSV) prefusion F protein vaccine (RSVpreF).

METHODS:

MATISSE was a phase 3, randomized, double-blinded, placebo-controlled trial. Healthy pregnant participants aged 49 years or younger at 24–36 weeks of gestation were randomized (1:1) to receive a single RSVpreF 120 micrograms or placebo dose. Primary efficacy endpoints included newborn and infant severe RSV-associated medically attended lower respiratory tract illness within 180 days after birth. The RSV-A and RSV-B serum neutralizing antibody titers were determined in a subset of pregnant participants and their newborns.

RESULTS:

In this final analysis, 7,420 pregnant participants were randomized, and 7,307 children were born (RSVpreF n=3,660, placebo n=3,647). Vaccine efficacy, defined as protection against newborn and infant severe RSV-associated medically attended lower respiratory tract illness, was 82.4% (95% CI, 57.5–93.9) and 70.0% (95% CI, 50.6–82.5) within 90 and 180 days of birth, respectively. The RSVpreF induced robust immune responses in pregnant participants and resulted in highly efficient transfer of maternal antibodies to their newborns across subgroups (by gestational age at delivery and at vaccination, number of days from vaccination to delivery, country, maternal age). Final RSVpreF safety results in pregnant and newborn and infant participants were consistent with the primary analysis with no new safety concerns identified.

CONCLUSION:

This final analysis of MATISSE trial data confirms the primary analysis conclusions: Maternal vaccination with RSVpreF has a favorable safety profile in both pregnant and newborn and infant participants and demonstrates efficacy against RSV-associated lower respiratory tract illness in infants through age 6 months. The RSVpreF induces robust immune responses in pregnant individuals, with corresponding high RSV-neutralizing titers in their newborns.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04424316.
Efficacy and safety of Treating Pulmonary Arterial Hypertension With Imatinib:A meta-analysis of randomized controlled trials
Authors: Chen Xiaofa , Xu Lina , Xue Bijuan
Published: January 2025

Pulmonary vascular remodeling and arterial hypertension (PAH) correlate to increased platelet-derived growth factor (PDGF) activity and elevated KIT expression. Imatinib has emerged as a potential therapeutic agent for PAH. The purpose of this systematic review and meta-analysis was to assess the effectiveness of imatinib in treatment of PAH. A literature search was conducted with the PubMed, Embase, Web of Science, and Cochrane Library to obtain randomized controlled trials (RCTs) where the efficacy of imatinib and placebo in PAH patients was compared. Three RCTs that involved 262 patients were finally included in this study. Results showed that imatinib significantly improved six-minute walk distance (MD = 42.76, 95% CI [9.20 - 76.32], P = 0.01), reduced pulmonary vascular resistance (MD = -396.68, 95% CI [-474.50 - -318.85], P < 0.00001), and lowered mean pulmonary arterial pressure (MD = -7.29, 95% CI [-13.97 - -0.61], P = 0.03) in PAH patients. No significant difference was found between the imatinib and placebo groups in terms of mortality (OR = 1.25, 95% CI [0.49 - 3.18]) or adverse events (OR = 1.82, 95% CI [0.76 - 4.36], P = 0.18). Despite the significant improvement of key hemodynamic parameters, there was no advantage in reducing clinical adverse events or mortality. The prolonged efficacy and safety of imatinib in PAH patients warrants further studies.
Preterm birth; current prevention strategies and challenges
Authors: Genzeb Ayele Siraye , Tsige Abate Wondesen
Published: January 2025

Preterm birth occurs when a baby is born alive before the full 37 weeks of pregnancy. Preterm delivery can occur spontaneously or be a sign that a doctor should schedule an early cesarean section or induction of labor. The purpose of this review was to advance our understanding of preterm birth and its preventive measures. This review examined the preterm birth epidemiology, risk factors, clinical evaluation, management, and preventive strategies. The primary maternal predisposing factors associated with preterm birth were birth defects, maternal infection, the presence of polymorphism genes, mothers of rural residents, mothers with a history of prior abortions, hypertensive disorders during pregnancy, low birth weight, elementary education level, and immigrants. To prevent preterm birth, pregnant women should receive counseling regarding a balanced diet, social drug usage, follow-up visits to medical facilities, and relaxation techniques. Some evidence suggests that low-dose aspirin and other cyclooxygenase inhibitors help prevent preterm birth in cases where traditional treatments are ineffective. More research will be necessary to enhance the outcomes of preterm birth care and reproductive health.
Slow-Coagulation Transscleral Cyclophotocoagulation in Pseudoexfoliation Glaucoma
Authors: Khodeiry Mohamed M. , Yusuf Ramsey , Dorizas Christopher A. , Elhusseiny Abdelrahman M. , Sayed Mohamed S. , Ruan Merry , Lee Richard K.
Published: January 2025

Purpose:

To evaluate the outcomes of slow-coagulation transscleral cyclophotocoagulation (SC-TSCPC) in pseudoexfoliation glaucoma (PXG).

Methods:

A single-center, retrospective non-comparative study including consecutive patients with medically uncontrolled PXG who underwent SC-TSCPC (1250-milliwatt power and 4-second duration). The primary outcome measure was surgical success (defined as intraocular pressure (IOP) between 6 - 21 mmHg with ≥20% reduction compared to baseline and no need for further glaucoma surgeries or development of vision-threatening complications). Success was considered qualified when achieved with additional glaucoma medications and complete when achieved without additional glaucoma medications. The secondary outcomes included IOP, glaucoma medication numbers, visual acuity, and postoperative complications at 1 and 2 years after laser treatment.

Results:

This study included 48 eyes of 48 patients. The median age of study participants was 87.5 years, with a median follow-up duration of 24.0 months. The qualified success for a single SC-TCPC treatment at 1 and 2 years was 58.3% and 47.9%, respectively. Cumulative qualified success (>1 SC-TSCPC) was 64.6% at 1 year and 56.2% at 2 years. Complete surgical success after a single SC-TSCPC was 45.8% at 1 year and 33.3% at 2 years, increased to 50.0% at 1 year and 39.6% at 2 years after >1 SC-TSCPC. After SC-TSCPC treatment, the mean IOP decreased from 29.2±10.3 mmHg on 3.7±1.0 medications pre-treatment to 14.3±6.43 mmHg on 2.6±1.3 medications at the final follow-up visit (P<0.001). Seven eyes (14.6%) had SC-TSCPC retreatment, and two eyes (4.2%) required incisional glaucoma surgeries. Reported postoperative complications included: decreased visual acuity in 9 (18.8%) eyes, iridocyclitis in 5 (10.4%) eyes, hyphema in 5 (10.4%) eyes, cystoid macular edema in 2 (4.2%) eyes, and transient hypotony in 2 (4.2%) eyes.

Conclusions:

SC-TSCPC is an effective, relatively safe, and repeatable surgical treatment option in PXG. Further prospective investigations are suggested to confirm these findings.
Peer review comments: Friend or foe?
Authors: Hicks Rodney W.
Published: January 2025

Peer review is a time-honored cornerstone of publishing. Peer reviewers, often blinded to the author, provide feedback to clarify the manuscript and validate the key messages and sciences. Authors may openly accept the feedback outright and make revisions. Authors may also view the feedback as intrusive and ill-mannered. Authors must revise the document promptly and consider each comment for merit. Tips for handling feedback are reviewed.
Metastasis-directed therapy in oligometastatic and oligoprogressive renal cell carcinoma
Authors: Dason Shawn , Wang Shang-Jui , Franceschelli Dominic , Singer Eric A.
Published: January 2025

Purpose of review

This review addresses the evolving role of metastasis-directed therapy (MDT) in the management of oligometastatic and oligoprogressive renal cell carcinoma (RCC). With advances in both surgical techniques and stereotactic ablative radiotherapy (SABR), it is timely to explore how MDT can improve patient outcomes in these distinct disease states. The review highlights the potential of MDT to delay systemic therapy and improve quality of life while noting the lack of randomized clinical trial data guiding its use.

Recent findings

Recent literature emphasizes the outcomes of MDT, including metastasectomy and SABR, in managing oligometastatic and oligoprogressive RCC. Key studies suggest that MDT may prolong progression-free survival and delay systemic therapy. SABR has demonstrated high local control rates and manageable toxicity, offering a less invasive alternative to surgery. Despite these findings, there remains uncertainty about MDT's long-term impact on overall survival due to the absence of prospective randomized trials.

MDT holds promise in treating RCC by offering symptom relief, improving quality of life, and potentially delaying systemic therapy. However, the long-term benefits, particularly regarding survival outcomes, remain unclear. Further research, including prospective trials, is needed to better define the role of MDT in clinical practice, particularly in the absence of clear guidelines for patient selection.
Examining the Association Between Public Health Accreditation and COVID-19 Outcomes
Authors: Davis Mary V. , Rider Nikki , Rashied Ammar A. , Bhat Shankar , Lang Britt
Published: January 2025

Objective:

To examine the association between local health department (LHD) accreditation and COVID-19 community outcomes, including rates of adult vaccination, hospitalization, and death.

Design:

We examined county level rates of adult vaccination, hospitalization, and death by LHD accreditation status over the course of the COVID pandemic. Additional independent variables included time period, COVID-19 Community Vulnerability Index (CCVI), state public health governance structure, and state policy environment. We used hierarchal linear mixed modeling with random intercept for county level data to account for repeated observations and fixed effects for all other variables.

Setting:

This study examined all communities in the United States of America.

Participants:

LHDs and the communities they serve.

Main Outcome Measures:

Rates of adult vaccination, hospitalization, and death due to COVID-19.

Results:

Among accredited LHDs, the adult population was more likely to be fully vaccinated when compared to unaccredited LHDs (P < .01). Additional variables in the model, which were also significant, included time period, CCVI, state policy environment, and state public health governance structure. There were no significant differences in the hospitalization rates in jurisdictions with an accredited LHD compared to jurisdictions where the LHD is not accredited. Death rates in jurisdictions with an accredited LHD were statistically significantly lower than death rates in jurisdictions where the health department was not accredited (P < .001). This relationship was significant with other key variables in the model, including time, CCVI, state policy environment, and state public health governance structure.

Conclusions:

This study demonstrates that there is an association between LHD accreditation and community health outcomes. Furthermore, we found that other factors, such as social determinants of health, state policy environment, and state public health governance structure impact community health outcomes.
Brief Report: Exploring PrEP Motivation as a Modifiable Target for HIV Prevention Uptake for Cisgender Women in Atlanta, Georgia
Authors: Anderson Katherine M. , Sheth Anandi N. , Sales Jessica M.
Published: January 2025

Background:

Pre-exposure prophylaxis for HIV prevention (PrEP) prescriptions in the United States have increased, yet only 15% of individuals assigned female at birth who could benefit from PrEP had received prescriptions as of 2022, with marked racial disparities.

Setting:

Georgia has the highest HIV incidence of any United States state, with more than half of new cases occurring in Atlanta. Accounting for approximately 1-in-5 cases, cisgender women living in Atlanta may benefit from clinic-based efforts to increase PrEP uptake.

Methods:

We enrolled 102 women from PrEP-providing family planning clinics in the Atlanta metro area. After the clinic visit, women self-completed a questionnaire and a staff-administered questionnaire. Surveys were repeated at 3 and 6 months; using baseline data only, we conducted bivariate analyses to determine factors associated with willingness to use PrEP.

Results:

Participants were primarily Black (87.5%) and aged ≥24 (54.5%) years. Women considered their risk of next-year HIV diagnosis (70%) and HIV risk (85.8%) to be low, despite 45% endorsing perception of at least slightly risky sexual behavior. Most women (59.4%) were willing to take PrEP, although few were planning or had started to take PrEP. Lifetime gonorrhea or Trichomonas diagnosis, perceived sexual risk, perceived high/moderate HIV risk, and more positive PrEP attitudes scores were associated with PrEP willingness, as were individual PrEP attitudes, concerns/barriers, and stigma items.

Conclusions:

Findings suggest modifiable constructs that could be used by providers as interventional targets with patients to increase PrEP uptake. We provide suggestions mapped onto the Stages of Change Model and PrEP care and motivation continua.
Risk of adverse birth outcomes and birth defects among women living with HIV on antiretroviral therapy and HIV-negative women in Uganda, 2015–2021
Authors: Serunjogi Robert , Mumpe-Mwanja Daniel , Williamson Dhelia M. , Valencia Diana , Namale-Matovu Joyce , Kusolo Ronald , Moore Cynthia A. , Nyombi Natalia , Kayina Vincent , Nansubuga Faridah , Nampija Joanita , Nakibuuka Victoria , Nelson Lisa J , Dirlikov Emilio , Namukanja Phoebe , Mwambi Kenneth , Williams Jennifer L , Mai Cara T , Qi Yan Ping , Musoke Philippa
Published: January 2025

Introduction:

We assessed the risk of adverse pregnancy and birth outcomes and birth defects among women living with HIV (WLHIV) on antiretroviral therapy (ART) and HIV-negative women.

Methods:

We analyzed data on live births, stillbirths, and spontaneous abortions during 2015–2021 from a hospital-based birth defects surveillance system in Kampala, Uganda. ART regimens were recorded from hospital records and maternal self-reports. Using a log-binomial regression model, we compared the prevalence of 16 major external birth defects and other adverse birth outcomes among WLHIV on ART and HIV-negative women.

Results:

A total of 203,092 births were included from 196,373 women of which 15,020 (7.6%) were WLHIV on ART. During pregnancy, 15,566 infants were primarily exposed to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART (n=13,614; 87.5%). After adjusting for maternal age, parity, and number of antenatal care (ANC) visits, WLHIV on NNRTI were more likely than HIV-negative women to deliver preterm (adjusted prevalence ratio [aPR]=1.27, 95% confidence interval [CI]: 1.21,1.32), post-term (aPR=1.23, 95% CI: 1.16,1.32), or small for gestational age infants (aPR=1.35, 95% CI: 1.30,1.40). Spina bifida was more prevalent among infants born to WLHIV on ART periconceptionally compared to HIV-negative women (aPR=2.45, 95% CI 1.27,4.33). The prevalence of the other selected birth defects were similar between infants from WLHIV on ART and HIV-negative women.

Conclusion:

In Uganda, WLHIV on ART were more likely than HIV-negative women to experience selected adverse birth outcomes. Further surveillance of maternal ART exposure, including by drug class and ART regimen, is needed to monitor and prevent adverse birth outcomes in WLHIV.
A Novel Technique With Buttress Plating for Comminuted Base Fractures of the Proximal Phalanx
Authors: Cha Soo Min , Nho Jae Hwi , Ga In Ho , Kim Yong Hwan
Published: January 2025

Background

Extra-articular but severely comminuted distal basal fractures of the proximal phalanx (PP) are rarely reported. Therefore, the aim of this study was to achieve proper union and desirable outcomes using low-profile locking plates/screws. We introduced our own surgical approach and reported the clinical/radiographic outcomes via retrospective case series.

Methods

Thirty-eight patients diagnosed with comminuted basal fracture of the PP were admitted between January 2014 and December 2020. Nineteen of these patients met the inclusion/exclusion criteria and were investigated in this retrospective study. Focusing only on preventing the volar tilt/collapse of the articular cartilage from the vertical position due to comminuted metaphysis, such as the “buttress concept by locking plate,” the defect was filled with bone grafts. Meticulous repair of the incised central tendon effectively stabilized it by tightening the sagittal band and capsule of the metacarpophalangeal joint. It also acted as an envelope with proper sealing to minimize the loss of grafted bone materials.

Results

Among the 19 patients, the mean patient age was 58.94 years, and the male/female ratio was 6:13. The mean follow-up period was 3.15 years, and the mean BMD was −0.15. Complete union was achieved after a mean of 9.63 weeks, without complications requiring secondary intervention. Two patients complained of skin lesion associated with PDS suture material, but this material spontaneously resolved by 4 weeks postoperatively. The mean extension lag at the proximal interphalangeal joint was 3.68 degrees, and the total active range of motion (TAM) was 256.38 degrees. Among the 19 patients, 6 were categorized as having a “good” modified Belsky classification, and the other patients all had an “excellent” classification. The mean articular-dorsal cortex angle was 85 ± 3.33 degrees at the final follow-up, which was slightly less than the normal value with statistical difference (P < 0.05); however, it did not correlate with the TAM statistically (r = 0.126, P = 0.608). Clinical outcomes were also satisfactorily evaluated using the VAS and DASH scores.

Conclusions

A low-profile locking plate is an effective option for extra-articular, severely comminuted basal fractures of the PP using the buttress concept in terms of clinical outcomes, such as finger movement and proper union.
Energetic shifts predict the mortality ofAnopheles gambiae
Authors: Zeferino Tiago G. , Silva Luis M. , Koella Jacob C.
Published: January 2025

Life history theory predicts that resource allocation adapts to ecological and evolutionary pressures. We investigated resource and energy dynamics in the malaria vectorAnopheles gambiaeafter exposure to two stressors: blood meals and infection by the microsporidianVavraia culicis. Our findings reveal the costs of blood feeding and parasitism on longevity, highlighting trade-offs in lifetime protein, carbohydrate, and lipid reserves. Notably, shifts in carbohydrate-to-lipid ratios predict survival likelihood, with survivors exhibiting higher resource reserves and uniquely transitioning from carbohydrate to lipid utilisation, a pattern absent in non-survivors. Through the integration of these results into ecological and epidemiological contexts, we discuss evolutionary constraints on reproduction and howPlasmodiumadapts to host resource availability. This study emphasises the coevolutionary dynamics between hosts and parasites and encourages future research on host physiological changes influenced by intrinsic and extrinsic factors.
Fast simulation of identity-by-descent segments
Authors: Temple Seth D , Browning Sharon R , Thompson Elizabeth A
Published: January 2025

The worst-case runtime complexity to simulate haplotype segments identical by descent (IBD) is quadratic in sample size. We propose two main techniques to reduce the compute time, both of which are motivated by coalescent and recombination processes. We provide mathematical results that explain why our algorithm should outperform a naive implementation with high probability. In our experiments, we observe average compute times to simulate detectable IBD segments around a locus that scale approximately linearly in sample size and take a couple of seconds for sample sizes that are less than ten thousand diploid individuals. In contrast, we find that existing methods to simulate IBD segments take minutes to hours for sample sizes exceeding a few thousand diploid individuals. When using IBD segments to study recent positive selection around a locus, our efficient simulation algorithm makes feasible statistical inferences, e.g., parametric bootstrapping in analyses of large biobanks, that would be otherwise intractable.
Changes in vaping trends since the announcement of an impending ban on
disposable vapes: a population study in Great Britain
Authors: Jackson Sarah E. , Shahab Lion , Tattan-Birch Harry , Buss Vera , Brown Jamie
Published: January 2025

Background/Aim

There has been a rapid rise in vaping prevalence among youth and young
adults in Great Britain since disposable vapes started to become popular in
2021. In January 2024, the government announced plans to introduce a number
of new vaping policies, including a ban on disposable vapes, to tackle youth
vaping. This study examined whether trends in current vaping and use of
disposable vapes have changed since this announcement.

Design, setting, and participants

Segmented regression analysis of data collected monthly between January
2022 and November 2024 as part of the Smoking Toolkit Study; a
representative household survey in Great Britain. We ran generalised
additive models using data from all participants aged ≥16y
(n=83,764; ‘adults’) and from a subset aged
16-24y (n=8,846; ‘young adults’).

Main outcome measures

Changes in trends in (i) the prevalence of current vaping and (ii) the
proportion of vapers mainly using disposable devices.

Results

Before January 2024, vaping prevalence was increasing by 24.5% per year
(RRtrend=1.245 [95%CI 1.193-1.299]) and use of
disposable vapes was increasing by 18.0% per year
(RRtrend=1.180 [95%CI 1.106-1.258]). These trends
changed after the new policy measures were announced
(RRΔtrend=0.718 [0.623-0.827] and
RRΔtrend=0.558 [0.460-0.677], respectively).
Instead of increasing, there was an uncertain decrease in vaping prevalence
from 13.7% [12.7-14.7%] in January 2024 to 12.4% [11.4-13.6%] in November
2024) and a substantial decline in the proportion of vapers mainly using
disposables from 43.7% [40.3-47.3%] to 30.8% [27.6-34.4%]. Similar changes
were observed among young adults (vaping prevalence:
RRΔtrend=0.647 [0.495-0.845]; use of disposable
vapes: RRΔtrend=0.526 [0.400-0.693]), with an uncertain
decline in vaping prevalence from 27.7% [24.5-31.3%] to 23.6% [20.2-27.6%]
between January and November 2024 and the proportion of vapers mainly using
disposables falling from 63.4% [59.0-68.2%] to 37.8% [32.3-44.2%].

Conclusions

Following the announcement of an impending ban on disposable vapes and
other potential vaping policies, recent increases in vaping prevalence in
Great Britain stalled – or may have even reversed – including among young
adults. In addition, there was a shift away from using disposable vapes,
with people increasingly opting to use devices that can be refilled and
recharged.
Peers over the past: Prior predation-risk experience does not dictate antipredator responses of individuals in groups
Authors: Rawat Kanika , Isvaran Kavita
Published: January 2025

Animals with predation-risk experiences can use the information to modulate their antipredator responses and survive future risk conditions (behavioural carryover). However, different contexts, such as sociality, may alter the risks and associated responses for an individual. A group can provide benefits to an individual, such as dilution of risk, confusion effect, and improved vigilance, potentially modifying carryover payoffs. Therefore, we tested the impact of sociality on the behavioural carryover of predation-risk experience. We usedAedes aegyptias a model system, where we had already established carryover, showing that predation-risk experience dictates future behaviour in a solitary setting. In contrast to solitary settings, we predicted that the behavioural carryover would not manifest in a group setting due to differences in trade-offs. We compared the behaviour of experienced and naive individuals in group settings in the presence and absence of an immediate threat. Our findings revealed that the past predation-risk experience did not influence the behaviour of individuals in a group setting. Instead, the immediate threat environment affected experienced and naive individuals similarly. These results suggest that the experience from predation past is more relevant when prey are solitary than when they are in a group due to the additional group advantages.
A new product containing secretome purified from bovine colostrum, Purasomes IRC100+, in the treatment of vaginal atrophy:in vitrostudy to evaluate safety and effectiveness
Authors: Salvaggio Antonio , Privitera Anna , Pennisi Stefania , Brundo Maria Violetta
Published: January 2025

Vaginal atrophy consists of the loss of elasticity and thinning of the vaginal tissues and mucous membranes. This is a condition that affects women especially during menopause, following the hormonal decline resulting from the cessation of ovarian activity. The objective of the present study was evaluated the effects of Purasomes IRC100+ on the proliferation and migration of VK2/E6E7 vaginal epithelial cells and on fibroblasts byin vitroexperiments. We tested three different concentrations (0.5%, 1% and 2%). We found that cell viability was highest at 2% Purasomes IRC100+ concentration for both cell lines. The scratch-wound assay was also done. Compared with the cell scratch at 0 h, cells in all groups migrated after 24 h, the scratch was significantly reduced in treated cells compared to untreated cells. In particular, the cell migration rates were 77% and 82%, respectively for VK2/E6E7 cells and fibroblasts treated with 2% of Purasomes IRC100+. Finally, this product promotes vaginal epithelial cell proliferation and therefore it could improve vaginal atrophy and vaginal wound healing.
The small genome size ensures adaptive flexibility for an alpine ginger
Authors: Xiao Qing-Song , Fér Tomáš , Guo Wen , Chen Hong-Fan , Li Li , Zhao Jian-Li
Published: January 2025

Understanding the proximate and ultimate causes of genome size (GS) variation is the focus of much research. However, the extent and causes of intraspecific variation in GS is debated and poorly understood. This study aims to test the large-genome constraint hypothesis through the variations of intraspecific GS. GS was measured in 53Roscoea tibeticapopulations from the Hengduan Mountains using flow cytometry. Stomatal size and density were collected from the wild populations and common garden populations. Associations between GS and environmental factors, stomatal traits were explored. We found that high GS variability was positively correlated with most environmental factors but negatively correlated with solar radiation during the growing season. The environment, rather than geography, significantly influenced the variations in GS. The stomatal traits measured in the wild were significantly correlated with GS, but no such correlations were detected in the common garden. Populations in the common garden have larger stomatal size and lower stomatal density. Populations with smaller GS present larger degree of stomatal traits variation from wild to common garden. Our findings suggests that intraspecific GS has experienced adaptive evolution driven by environmental stress and the evolution of intraspecific GS can be explained by the large-genome constraint hypothesis. Smaller GS is more advantageous to the alpine ginger to adapt to alpine habitat and thrive in changing habitat.
Peptidisc-assisted hydrophobic clustering towards the production of multimeric and multispecific nanobody proteins
Authors: Duong Franck , Chen Yilun
Published: January 2025

Protein multimerization is a powerful engineering strategy for enhancing structural stability, diversity and functional performance. Typical methods to cluster proteins include tandem linking, fusion to self-assembly domains and cross-linking. We present here an approach that leverages the peptidisc membrane mimetic to stabilize hydrophobic-driven protein associations. We apply the method to nanobodies (Nbs), effective substitutes to antibodies due to their production efficiency, cost effectiveness, and lower immunogenicity, and we demonstrate the formation of multimeric assemblies termed "polybodies" (Pbs). Starting with Nbs directed against the green fluorescent protein (GFP), we produce Pbs that display increased affinity for GFP due to the avidity effect. The benefit of avidity in affinity-based assays is also demonstrated using moderate-affinity Nbs against human serum albumin. With the same auto-assembly principle, we produce bispecific and auto-fluorescent Pbs, validating our method as a versatile and general engineering strategy to generate multispecific and multifunctional protein entities. Peptidisc-assisted hydrophobic clustering thus expands the protein engineering toolbox to broaden the scope of protein multimerization in life sciences.
PRC1 resists microtubule sliding in two distinct resistive modes due to variations in the separation between overlapping microtubules
Authors: Steckhahn Daniel , Fiorenza Shane , Tai Ellinor , Forth Scott , Kramer Peter R , Betterton Meredith
Published: January 2025

The elongation rate of the mitotic spindle is tightly regulated by microtubule crosslinking proteins. For example, PRC1, a non-motor member of the MAP65 family, crosslinks microtubules in an antiparallel configuration to assemble the spindle midzone. PRC1 has also been found to resist microtubule sliding via two distinct resistive modes: a braking mode in which microtubule sliding is significantly impeded and a coasting mode in which PRC1 lightly resists sliding. To explore possible molecular-scale mechanisms, we developed a computational model of sliding microtubule pairs crosslinked by PRC1 that reproduces the braking and coasting modes observed experimentally. We found that the braking mode was associated with a substantially smaller lateral separation between the crosslinked microtubules than the coasting mode. This closer separation aligns the PRC1 force against sliding, increasing the resistive PRC1 force and dramatically reducing sliding speed. The model also shows that higher initial sliding speed favors the transition to braking, resulting in an average sliding speed due to PRC1 resistance that is similar across variation in the unhindered microtubule sliding speeds. Further, our results highlight the importance of the geometric relationships between crosslinkers and microtubules, which may extend to other systems.