bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosomal-Level Genome Assembly of the Antarctic Sea Urchin Sterechinus neumayeri: A Model for Antarctic Invertebrate Biology
Authors: Warner Jacob F , Range Ryan C , Fenner Jennifer , Ka Cheikouna , Waits Damien S , Boddy Kristen , David Kyle T , Mahon Andrew R , Halanych Kenneth M
Published: October 2024

The Antarctic sea urchin Sterechinus neumayeri (Echinoida; Echinidae) is routinely used as a model organism for Antarctic biology. Here, we present a high-quality genome of S. neumayeri. This chromosomal-level assembly was generated using PacBio long-read sequencing and Hi-C chromatin conformation capture sequencing. This 885.3-Mb assembly exhibits high contiguity with a scaffold length N50 of 36.7 Mb assembled into 20 chromosomal length scaffolds. These putative chromosomes exhibit a high degree of synteny compared to other sea urchin models. We used transcript evidence gene modeling combined with sequence homology to identify 21,638 gene models that capture 97.4% of BUSCO orthologs. Among these, we were able to identify and annotate conserved developmental gene regulatory network orthologs, positioning S. neumayeri as a tractable model for comparative studies on evolution and development.
Performance evaluation of evaporator coil of a domestic refrigerator under frosting
Authors: Kumar Manav , Kiran Kumar K , Mondal Sharifuddin , Khan Mohammad Amir , Khan T M Yunus , Almakayeel Naif , Khan Wahaj Ahmad
Published: October 2024

The frost deposition on the outer exterior of the evaporator coil degrades the thermal performance by building up the thermic resistance and the pressure drop across the air side. In this study, numerical performance investigations of domestic refrigerator evaporator coil in frosted condition are presented. For this purpose, evaporator coil having two kinds of fin configurations such as plain and wavy in staggered tube arrangement is considered. The mass, momentum, and energy equations along with empirical correlations are employed for simultaneous transfer of heat and mass during the process. The air-side parameters, such as air flow rate and relative humidity, are varied whilst cooling fluid-side parameters are kept fixed. The cooling fluid is selected as the commonly used haloalkane refrigerant (R-134a) in domestic refrigerators. The numerical analyses are carried out for 2 h working and the effect on growing frost and its density is noted. It is found that total conductivity (UA) decreases 15.6% and 14.2% and air-side pressure drop increases by 99% and 84.3%, respectively, for two considered fin configurations—plain and wavy. The minimum free flow area is reduced by 29.6%.
Detection of Soybean GMO Events Using Two Multiplex Droplet Digital PCR Assays
Authors: Demeke Tigst , Eng Monika
Published: October 2024

Background

Detection methods for GMO events are required because of regulatory compliance requirements. Efficient detection and quantification of GMO events saves time and resources. Multiplex digital PCR (dPCR) allows detection and quantification of more than one GMO event at the same time.

Objective

The study used two tetraplex droplet digital PCR (ddPCR) assays for the detection of 19 soybean GMO events.

Methods

Two multiplex dPCR assays were developed and optimized for the detection of 19 soybean GMO events. The first tetraplex ddPCR assay contained four element-specific targets commonly found in GMO plants (P-35S, T-nos, tE9, and Pat). The second event-specific tetraplex ddPCR assay targeted four soybean GMO events that are not detected with the element-specific tetraplex ddPCR (CV127, DP305423, MON87701, and MON87751).

Results

The element-specific tetraplex ddPCR assay detected all the expected 15 soybean GMO events. The element-specific tetraplex ddPCR assay also detected selected soybean GMO events at the 0.01% level. The event-specific tetraplex ddPCR assay was successfully used to quantify the four soybean GMO events at the 0.1, 1, 2, and 5% levels. The event-specific tetraplex ddPCR assay also detected the four soybean GMO events at the 0.01% level.

Conclusions

The two tetraplex ddPCR assays can be used for the detection of 19 soybean GMO events.

Highlights

An element-specific tetraplex ddPCR assay was used to detect 15 soybean GMO events, and an event-specific tetraplex ddPCR assay was used to detect and quantify four soybean GMO events that are not detected by the element-specific ddPCR assay.
Late gestation maternal infection with bovine viral diarrhea virus impacts offspring feedlot performance, digestion, blood parameters, and hot carcass weights
Authors: Engle Terry E , Guimaraes Octavio , Loh Huey Yi , Thorndyke Meghan P , Van Campen Hana , Kincade Jessica N , Eder Jordan M , Hansen Thomas R
Published: October 2024

Fetal infection with bovine viral diarrhea virus (BVDV) after 150 d results in transient fetal infections (TI). Twenty-five unvaccinated, yearling Hereford heifers, seronegative for antibodies to BVDV1 and BVDV2, were bred by artificial insemination with X chromosome-bearing sperm from 1 Angus sire to examine the impact of TI on postnatal growth, estimated dry matter digestibility, blood parameters, and carcass characteristics. On day 175 of pregnancy, dams were intranasally inoculated with either sham control or 4.0 log median tissue culture infectious dose noncytopathic type2 BVDV to generate control or TI offspring, respectively. All control dams remained seronegative and all BVDV-inoculated dams seroconverted by day 14 post-inoculation. All control offspring were seronegative and all TI offspring were seropositive for antibodies to type 2 BVDV at birth. All offspring were raised on pasture until weaning. At weaning, all calves were transported to our research feedlot facility, housed in 3 pens, and transitioned to a high-energy concentrate-based diet. Heifer body weights (BW) and jugular blood samples were collected every 28 d. On day 84 of the feeding period, titanium dioxide was added to the diet of 12, age-paired, individually fed, heifers (6 control and 6 TI heifers; approximately 1 yr of age) for 28 d and used to estimate dry matter digestibility. On days 105 and 240 ruminal fluid (approximately 900 mL) was collected from every animal using a stomach pump and analyzed for short-chain fatty acids (SCFA). After approximately 287 d on feed, heifers were transported to a USDA-inspected abattoir and harvested. TI heifers had lighter final BW (P < 0.04) when compared to control heifers. Average daily gain was greater (P < 0.01) in control compared to TI heifers. TI heifers had a 2.2% lesser (P < 0.05) apparent dry matter digestibility, lighter (P < 0.01) hot carcass weights, but similar ruminal SCFA compared to controls. Blood glucose concentrations were similar (P > 0.8) between control and TI heifers. Ceruloplasmin activity (P < 0.03) and the oxidized form of glutathione (GSSG; P < 0.01), indicators of chronic inflammation, were increased in plasma from TI heifers compared to controls. Other indicators of oxidative stress were not impacted (P > 0.10) by TI status. These data suggest that fetal BVDV transient infection negatively impacts growth throughout the feeding period, possibly by impacting gastrointestinal tract function and increasing systemic inflammation.
Topical steroid use for suppression of hypergranulation in burns: Trends across the Atlantic
Authors: Shoham Yoram , Comish Paul , Tsur Rotem , Silberstein Eldad , Krieger Yuval , Eliav Tal , Cleary Michelle , Kornhaber Rachel , Goverman Jeremy
Published: October 2024

Hypergranulated wounds from thermal injury remain a complex and debilitating problem for burn patients. Currently, there is no standard therapy to prevent or treat hypergranulation following burn injury. Many centers use topical corticosteroids; however, their use seems to be geographically dependent and controversial. The primary aim of this study was to quantify the current use of topical corticosteroids for post-burn hypergranulation in North America (NA) and Europe, while secondarily assessing for perceptions of safety and efficacy. We designed a survey that was distributed to the members of the European and American Burn Associations. Data was extracted and analyzed using SPSS software. A total of 165 respondents completed the survey (90 and 75 for the European and NA members, respectively). Seventy-one of the 90 (78.9%) European respondents reported they routinely use topical steroids for suppression of hypergranulation tissue in burns, versus 25 of the 75 (33.3%) NA respondents (p<0.001). European respondents, compared to NA respondents, were significantly more likely to consider topical steroid use safe (100% vs. 74.4%, p <0.001) and effective (98.6% vs. 66.7%, p < 0.001) for treatment of hypergranulated burn wounds. There was no significant difference in reported systemic effects seen after topical steroid use when comparing NA respondents and European respondents (6.5% vs. 6.9%, p > 0.10). The results of this study suggest that the use of steroids for hypergranulation tissue in burn care is more prevalent in Europe than NA, which may be due to discordant views on safety and efficacy despite minimal reported adverse effects.
Use digital rock physics to characterize velocity and attenuation signatures of deep cavity-fracture carbonate reservoirs
Authors: Liu Weihua , Zhao Luanxiao , Qiu Xuangan , Wang Yirong , Wang Yang , Zhu Wei
Published: October 2024

Conventional rock physics experiments and well logging analyses face challenges in deep carbonate formation containing meter-scale cavity-fracture system, since it is unfeasible to extract representative samples from targeted formation. In this study, differing from the conventional digital rock models at the core scale, we construct a digital rock model from realistic outcrop images with meter-scale heterogeneity of cavities and fractures. Using a dynamic stress–strain simulation, we investigate how reservoir type, fracture density and spacing, cavity porosity and size, fluid saturation, and connectivity influence wave dispersion and attenuation. By selecting the simulation frequency of 0.3 MHz approximately corresponding to the field seismic measuring frequency of 30 Hz, the simulation results can reflect the realistic seismic velocity and attenuation characteristics of deep carbonate reservoir rocks. We find that the P-wave velocity decreases linearly with increasing fracture and cavity porosity. The P-wave attenuation is sensitive to variations in fracture density but shows limited sensitivity to changes in cavity porosity and size. Fractures with narrower spacing result in higher attenuation when fracture density remains constant. Deep carbonate rocks with cavity-fracture systems saturated with two immiscible fluids display enhanced attenuation compared to fully saturated conditions. The velocity demonstrates an almost linear increase with water saturation, while attenuation initially increases before decreasing at a peak water saturation of 70%–80%. The connectivity between fractures and cavities significantly influences the attenuation behavior. Our simulation results provide valuable guidance for seismic data processing and interpretation of deep carbonate reservoir rocks with cavity-fracture systems.
Low-grade postoperative spine infection with a history of oral cavity infections: think of Peptoniphilus asaccharolyticus
Authors: Zygogiannis Konstantinos , Pappa Eleni , Antonopoulos Spiridon , Chatzikomninos Ioannis , Kalampokis Anastasios
Published: October 2024

Peptoniphilus asaccharolyticus is a typical gram-positive commercial microorganism of the skin that depending on the occasion can also be detected in the gut and in the genitourinary system. There is a paucity in the literature regarding the role of P. asaccharolyticus in spine infections and the potential impact in postoperative implications. A case report of a patient suffering from infection of spinal instrumentation of the uncommon pathogen above is presented.
Sensitization of melanoma cells to standard chemotherapy: G-quadruplex binders as synergistic agents
Authors: Persico Carolina , Iaccarino Nunzia , Romano Francesca , Giustiniano Mariateresa , Russo Camilla , Laneri Sonia , Di Lorenzo Ritamaria , Aiello Immacolata , Abate Sara , Izzo Luana , Merlino Francesco , Brancaccio Diego , Pagano Bruno , Amato Jussara , Marzano Simona , D’Aria Federica , De Tito Stefano , Di Porzio Anna , Randazzo Antonio
Published: October 2024

The use of chemotherapeutics has achieved considerable success in cancer therapy; however, their toxicity can severely impact patients’ health. In this study, aiming to reduce the doses and potential side effects of traditional chemotherapeutics, we systematically treated A375MM human melanoma cells with seven clinically approved antineoplastic drugs, in combination with three well-characterized G-quadruplex (G4) ligands, using either simultaneous or sequential dosing schedules. Interestingly, the G4 binders synergized with most of the investigated anticancer drugs, with the degree of synergism being strictly dependent on both the treatment schedule and the drug sequence employed. Notably, some of the synergistic combinations showed selective toxicity toward melanoma cells over nontumorigenic human keratinocytes. Furthermore, immunofluorescence experiments highlighted the potential implication of G4 structures in the molecular mechanisms driving the synergistic interaction between some chemotherapeutics and G4 binders. Overall, our systematic study supports the combination of G4-interacting molecules with standard antineoplastic drugs as a promising antitumor strategy.
CAF to the Rescue! Potential and Challenges of Combination Antifungal Therapy for Reducing Morbidity and Mortality in Hospitalized Patients With Serious Fungal Infections
Authors: Jacobs Samantha E , Chaturvedi Vishnu
Published: October 2024

The global burden of invasive fungal disease is substantial and escalating. Combination antifungal therapy (CAF) may improve patient outcomes by reducing development of resistance, improving drug penetration and rate of fungal clearance, and allowing for lower and less toxic antifungal drug doses; yet, increased cost, antagonism, drug-drug interactions, and toxicity are concerns. Clinical practice guidelines recommend antifungal monotherapy, rather than CAF, for most invasive fungal diseases due to a lack of comparative randomized clinical trials. An examination of the existing body of CAF research should frame new hypotheses and determine priorities for future CAF clinical trials. We performed a systematic review of CAF clinical studies for invasive candidiasis, cryptococcosis, invasive aspergillosis, and mucormycosis. Additionally, we summarized findings from animal models of CAF and assessed laboratory methods available to evaluate CAF efficacy. Future CAF trials should be prioritized according to animal models showing improved survival and observational clinical data supporting efficacy and safety.
Real-world effectiveness of palbociclib plus endocrine therapy in HR+/HER2− advanced breast cancer: final results from the POLARIS trial
Authors: Tripathy Debu , Blum Joanne L , Karuturi Meghan S , McCune Steven , Kurian Sobha , Moezi Mehdi , Anderson Daniel , Gauthier Eric , Zhang Zhe , Montelongo Monica Z , Wang Yao , Rocque Gabrielle B
Published: October 2024

Background

Strict eligibility criteria for participation in randomized clinical trials (RCTs) often limit the generalizability of data when applied to a more heterogeneous real-world population. Thus, evidence generated directly from real-world populations, including subgroups underrepresented in RCTs, can help inform routine clinical practice. POLARIS (NCT03280303), a prospective, observational, multicenter, cohort study, evaluated patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC) receiving palbociclib + endocrine therapy (ET) in routine care.

Methods

Demographics, baseline characteristics, and treatment patterns were summarized descriptively. Real-world response and clinical benefit rates, real-world progression-free survival (rwPFS), and overall survival (OS) were summarized descriptively by line of therapy and endocrine partner in the overall cohort and various subgroups.

Results

Between January 2017 and October 2019, 1250 patients (median age of 64.0 years) initiated treatment with palbociclib-based therapy, including 901 in the first-line (1L) setting and 349 in the second-line or later (≥2L) settings. Real-world response and clinical benefit rates with palbociclib + ET were 34.0% and 69.4%, respectively, in 1L, and 21.8% and 57.9% in ≥2L. Median rwPFS was 20.9 (95% CI, 18.7-24.7) and 13.5 (10.6-17.1) months, and median OS was 48.5 (42.0-not estimable) and 37.2 (31.2-40.8) months, with 1L and ≥2L palbociclib + ET, respectively.

Conclusions

Outcomes in this large, heterogeneous, real-world population are generally consistent with previously reported results from clinical trials and other real-world studies, further supporting the use of palbociclib + ET in patients with HR+/HER2− ABC.

Trial registration

NCT03280303 (ClinicalTrials.gov).
Using native and synthetic genes to disrupt inositol pyrophosphates and phosphate accumulation in plants
Authors: Freed Catherine , Craige Branch , Donahue Janet , Cridland Caitlin , Williams Sarah Phoebe , Pereira Chris , Kim Jiwoo , Blice Hannah , Owen James , Gillaspy Glenda
Published: October 2024

Inositol pyrophosphates are eukaryotic signaling molecules that have been recently identified as key regulators of plant phosphate sensing and homeostasis. Given the importance of phosphate to current and future agronomic practices, we sought to design plants, which could be used to sequester phosphate, as a step in a phytoremediation strategy. To achieve this, we expressed diadenosine and diphosphoinositol polyphosphate phosphohydrolase (DDP1), a yeast (Saccharomyces cerevisiae) enzyme demonstrated to hydrolyze inositol pyrophosphates, in Arabidopsis thaliana and pennycress (Thlaspi arvense), a spring annual cover crop with emerging importance as a biofuel crop. DDP1 expression in Arabidopsis decreased inositol pyrophosphates, activated phosphate starvation response marker genes, and increased phosphate accumulation. These changes corresponded with alterations in plant growth and sensitivity to exogenously applied phosphate. Pennycress plants expressing DDP1 displayed increases in phosphate accumulation, suggesting that these plants could potentially serve to reclaim phosphate from phosphate-polluted soils. We also identified a native Arabidopsis gene, Nucleoside diphosphate-linked moiety X 13 (NUDIX13), which we show encodes an enzyme homologous to DDP1 with similar substrate specificity. Arabidopsis transgenics overexpressing NUDIX13 had lower inositol pyrophosphate levels and displayed phenotypes similar to DDP1-overexpressing transgenics, while nudix13-1 mutants had increased levels of inositol pyrophosphates. Taken together, our data demonstrate that DDP1 and NUDIX13 can be used in strategies to regulate plant inositol pyrophosphates and could serve as potential targets for engineering plants to reclaim phosphate from polluted environments.
The structure of a Tau fragment bound to tubulin prompts new hypotheses on Tau mechanism and oligomerization
Authors: Ammar Khodja Liza , Campanacci Valérie , Lippens Guy , Gigant Benoît
Published: October 2024

Tau is a protein involved in the regulation of axonal microtubules in neurons. In pathological conditions, it forms filamentous aggregates which are molecular markers of neurodegenerative diseases known as tauopathies. Structures of Tau in fibrils or bound to the microtubule have been reported. We present here a structure of a Tau construct comprising the PHF6 motif, an oligopeptide involved in Tau aggregation, as a complex with tubulin. This Tau fragment binds as a dimer to a new site which, when transposed to the microtubule, would correspond to a pore between protofilaments. These results raise new hypotheses on Tau-induced microtubule assembly and stabilization and on Tau oligomerization.
Extremal Rotating BTZ Black Holes Cannot Be Dressed in (anti-)Self-Dual Maxwell Field
Authors: Maeda Hideki , Podolský Jiří
Published: October 2024

Under the (anti-)self-dual condition for orthonormal components of the Faraday tensor, the 3D Einstein–Maxwell system with a negative cosmological constant $\Lambda$ admits a solution obtained by Kamata and Koikawa and later by Cataldo and Salgado in the most general form. Actually, Clément first obtained this solution and interpreted it as a regular particle-like solution without horizon. Nevertheless, it has been erroneously stated in some literature that this Clément–Cataldo–Salgado (CCS) solution, locally characterized by a single parameter, describes a black hole even in the charged case as it reduces to the extremal rotating Bañados–Teitelboim–Zanelli (BTZ) solution in the vacuum limit and its curvature invariants are constant. In this paper, we supplement Clément’s interpretation by showing that there appears a parallelly propagated curvature singularity corresponding to an infinite affine parameter along spacelike geodesics at the location of the Killing horizon in the extremal rotating BTZ solution when the (anti-)self-dual Maxwell field is added. If the spatial coordinate $\theta$ is periodic, closed timelike curves exist near the singularity. It is also shown that the CCS solution is of Cotton type N (in contrast to charged rotating BTZ black holes which are of type I away from the horizon), and the energy-momentum tensor of the Maxwell field is of Hawking–Ellis type II. The metric solves the Einstein-$\Lambda$ equations also with a massless scalar field or a null dust fluid. We explicitly demonstrate that it belongs to the Kundt shear-free, nontwisting, and nonexpanding class of geometries, whereas extremal rotating BTZ black holes have expanding principal null directions. It means that the CCS metric represents the specific null (i.e. “radiative”) Maxwell field generated by a singular source, rather than an extremal rotating BTZ black hole dressed in an (anti-)self-dual Maxwell field.
Chief medical officers in the United Kingdom: maintaining ‘independence’ inside government
Authors: Smith Katherine E , Macintyre Anna , MacAulay Margaret , Fafard Patrick
Published: October 2024

Background

The Chief Medical Officer (CMO), one of the UK’s most senior public health leadership roles, was crucial in supporting policymakers in responding to COVID-19. Yet, there exist only a handful of (largely historical) accounts of the role in England. This article is the first to empirically examine how the scope, focus and boundaries of the CMO role vary over time across the four UK nations, including during public health emergencies.

Methods

We undertook semi-structured interviews with 10 current and former CMOs/Deputy CMOs in the four UK nations and analysed relevant documents.

Findings

The CMO role is not clearly defined in contemporary UK legislation and is instead shaped by iterative policies, incumbent preferences, and organizational needs, leading to variation over time and between nations. Nonetheless, most participants framed the role as primarily providing ‘independent’ advice to government despite being senior civil servants who, in communicating with the public, sometimes speak ‘on behalf’ of government.

Conclusions

The flexibility of UK CMO roles allows for responsive adaption but poses risks for how well these roles are understood. A potential tension between providing ‘independent’ policy advice and a need to publicly communicate government policies and guidelines may be exacerbated in emergency contexts.
Not Just They/Them: Exploring Diversity and Meaning in Pronoun Use among Non-Binary Individuals
Authors: Moeder Jessica , Scarborough William J , Risman Barbara
Published: October 2024

Gender-neutral pronouns, such as they/them, have been studied as a site of identity affirmation and, at other times, contestation for non-binary individuals. In this study, we draw from interviews with 123 non-binary individuals to better understand the role of pronouns in these individuals’ lives. We find that pronoun practices are ontoformative—they actively (re)construct the meanings attached to gender and gender identities. Yet, not all non-binary individuals use similar pronoun practices, resulting in diverse ontologies of non-binary identity. Half of our respondents consistently used non-binary pronouns, such as they/them, and felt they were a stable and direct reflection of identity—an approach we refer to as a fixed expression. These individuals define non-binary gender as independent from the woman/man binary. The other half of our sample held flexible pronoun expressions—they used multiple pronouns and anticipated future changes. Some of these individuals rejected the idea that pronouns expressed their identity, offering a definition of non-binary that eschewed categorical distinctions. Others embrace pronouns as identity expressing and forming, but felt that multiplicity best reflected their identity, offering a definition of non-binary as category-spanning. Our findings highlight the central and diverse role of pronouns in the social construction of non-binary ontology.
Uterine carcinosarcoma: Unraveling the role of epithelial‐to‐mesenchymal transition in progression and therapeutic potential
Authors: Gopinatha Pillai Mohan Shankar , Shaw Pallab , Dey Bhowmik Arpan , Bhattacharya Resham , Rao Geeta , Dhar Dwivedi Shailendra Kumar
Published: October 2024

Uterine carcinosarcoma (UCS) is a rare and highly aggressive gynecological malignancy characterized by poor prognosis. Due to its rarity, UCS remains relatively unexplored, and specific treatment guidelines are scarce. Despite standard treatments, including surgery, adjuvant chemotherapy, and radiotherapy, UCS has a high recurrence rate and poor overall prognosis. The aggressive nature of UCS is attributed to the metaplastic transformation of carcinomatous elements into sarcoma. This “biphasic” neoplasm features a mixture of epithelial and mesenchymal/tumor components, which partially share molecular signatures and exhibit a typical epithelial‐to‐mesenchymal transition (EMT) gene expression profile. Recent scientific advancements have highlighted the pivotal role of EMT in UCS progression and mortality. This review covers the epidemiology of UCS, theories regarding its origin, and the current state of clinical trials with more emphasis on the role of EMT drivers in UCS progression and scope of targeting these molecules. By shedding light on the molecular mechanisms supporting UCS, particularly emphasizing the importance of EMT, we aim to provide a more comprehensive understanding of the disease to support the development of more effective therapeutic strategies.
Efficacy and safety of tegoprazan (LXI-15028) vs. esomeprazole in patients with erosive esophagitis: A multicenter, randomized, double-blind, non-inferiority phase Ⅲ trial
Authors: Zhu Huiyun , Xue Qian , Song Yingxiao , Zhang Zhenyu , Li Xing , Lyu Shengxiang , Zhan Qiang , Liu Fei , Lu Lungen , Zhong Liang , Chen Weixing , Shao Dong , Ding Yanbing , Liu Deliang , Yang Xiaozhong , Huang Zhiming , Li Zhaoshen , Du Yiqi
Published: October 2024

Background:

An evidence gap still exists regarding the efficacy and safety of tegoprazan in Chinese patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China.

Methods:

This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement.

Results:

A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: −1.7, 95% confidence interval [CI]: −8.5, 5.0, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients’ diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively.

Conclusion:

Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Trial Registration:

ClinicalTrials.gov, NCT03615677.
Safety and Efficacy of Neoadjuvant Docetaxel and Radiotherapy in Localized High-Risk Prostate Cancer
Authors: Ohaegbulam Kim C. , Post Carl M. , Farris Paige E. , Garzotto Mark , Beer Tomasz M. , Hung Arthur , Williamson Casey W.
Published: October 2024

Objectives:

Approximately 15% of patients with localized prostate cancer are at high risk for disease recurrence. Many clinical trials have evaluated the impact of neoadjuvant therapy before radical prostatectomy with mixed results (NCT00321698).

Methods:

This phase I/II clinical trial evaluated the tolerability and preliminary efficacy of neoadjuvant radiation therapy and docetaxel before prostatectomy in 25 men with high-risk prostate cancer. The treatment regimen included 45 Gy radiotherapy in 25 fractions to the prostate and seminal vesicles over 5 weeks, along with weekly dose-escalated docetaxel up to 30 mg/m², followed by prostatectomy and bilateral lymph node dissection. The primary endpoint was the rate of pathologic complete response (pCR). Secondary endpoints included adverse events, symptom and quality of life measures, and prostate-specific antigen metrics.

Results:

All 25 patients completed the planned treatment. The primary endpoint of pCR was not achieved. Lymphopenia was the most common grade 3 or higher toxicity, with no grade 3 or higher genitourinary or gastrointestinal toxicities observed. With a median follow-up of 11.6 years, the 10-year biochemical recurrence-free survival was 60%, and distant metastasis-free survival was 80%. Prostate cancer-specific survival and overall survival at 10 years were 84% and 60%, respectively.

Conclusions:

Although pCR was not met, the treatment demonstrated a modest toxicity profile and reasonable long-term outcomes, suggesting feasibility and safety. Further studies are needed to optimize endpoints and assess the efficacy of neoadjuvant treatments compared with standard approaches in high-risk prostate cancer patients.
Mechanisms coupling lipid droplets to MASLD pathophysiology
Authors: Reid Mari V. , Fredickson Gavin , Mashek Douglas G.
Published: October 2024

Hepatic steatosis, the buildup of neutral lipids in lipid droplets (LDs), is commonly referred to as metabolic dysfunction–associated steatotic liver disease when alcohol or viral infections are not involved. Metabolic dysfunction–associated steatotic liver disease encompasses simple steatosis and the more severe metabolic dysfunction–associated steatohepatitis, characterized by inflammation, hepatocyte injury, and fibrosis. Previously viewed as inert markers of disease, LDs are now understood to play active roles in disease etiology and have significant nonpathological and pathological functions in cell signaling and function. These dynamic properties of LDs are tightly regulated by hundreds of proteins that coat the LD surface, controlling lipid metabolism, trafficking, and signaling. The following review highlights various facets of LD biology with the primary goal of discussing key mechanisms through which LDs promote the development of advanced liver diseases, including metabolic dysfunction–associated steatohepatitis.
Observation of Two Novel mcr-10.1–Carrying Plasmids in Clinical Escherichia coli Strains
Authors: Liu Zhaopeng , Zheng Xinrou , Nan Congcong , Xu Jihua , Zhu Jiaming , Li Ling , Wang Mingyu , Wang Wenjia , Shen Wenlong
Published: October 2024

Polymyxins are a class of last-resort antibiotics used to treat infections caused by multidrug-resistant bacteria. Mobile resistance determinants for polymyxins, including mcr-1 to mcr-10 genes, have previously been reported. Among them, mcr-10 has commonly been observed in Enterobacter and Klebsiella species. However, the presence of mcr-10 in Escherichia coli, an important opportunistic pathogen, has rarely been reported. This work describes the observation of mcr-10.1 in two clinical E. coli strains, with mcr-10.1 hosted on two novel plasmids, one of which carries transconjugation genes. These strains were isolated from anal fistula–suffering patients, suggesting their close relation to human bacterial infection. The genetic context of mcr-10.1 was also found to differ from those previously identified in E. coli strains. This work is the first observation of mcr-10.1–carrying E. coli in clinical settings, expanding our knowledge of this important antibiotic resistance gene.
New Insights Into the Molecular Characteristics of Binary Toxin-Producing Clostridioides difficile Strains in China: A Comparative Genomics Study
Authors: Wu Tao , Bi Xiajing , Zhao Yuhong , Lv Tao , Zhou Yizheng , Zheng Lisi , Shen Ping , Zhu Danhua , Chen Yunbo
Published: October 2024

Binary toxin (CDT)-producing Clostridioides difficile is associated with severe clinical symptoms and high mortality rates. However, the fundamental genomic factors that underpin the differentiated prevalence of CDT-producing C. difficile strains in China remain to be elucidated. To provide a comprehensive view of the genetic characteristics, this study comprehensively analyzed whole-genome sequences of CDT-producing C. difficile strains from China. The number of unique accessory genes in sequence type (ST)-5 strains, which are predominant in China, increased steadily with the increasing number of genomes sampled, while the accumulation curve for ST-1 strains was shallower. This suggests that ST-5 may have an open pangenome, whereas ST-1 may have a relatively conservative and stable pangenome. The pathogenicity locus (PaLoc) variants of Clades 1, 2 and 5 were found to share a common genetic organization, with the CDT locus (CdtLoc) showing lower variability than PaLoc. PaLoc in Clade 3 exhibits an insertion of transposon Tn6218, which is clade-specific. The flexibility of the C. difficile accessory genome has facilitated the development of divergent lineages characterized by the presence of evolutionarily advantageous genetic traits. This genetic diversification has led to enhanced antimicrobial resistance, increased virulence and improved metabolic capacities, which collectively augment the ability of C. difficile to survive and proliferate.
Can Benzimidazole Resistance Undermine the Philippines’ Success in Controlling and Eliminating Soil-Transmitted Helminth Infections? A Mini-Review
Authors: Tenorio Jan Clyden B. , Belizario Vicente Y. , Furtado Luis Fernando Viana , Suttiprapa Sutas
Published: October 2024

Soil-transmitted helminth (STH) infections remain a significant global health burden, affecting over 1.5 billion people worldwide. In the Philippines, STH infections continue to be prevalent, despite ongoing control efforts. The Integrated Helminth Control Program, whose cornerstone is the mass drug administration with benzimidazole drugs, has shown some success in reducing STH prevalence in the country. However, the persistence of infection prevalence being above the national and global targets and the potential for benzimidazole resistance have raised concerns about the long-term sustainability of current control strategies. This review examines the development of benzimidazole resistance in STH, focusing on the role of single nucleotide polymorphisms in the β-tubulin isotype that alter the protein’s amino acid composition, thereby negatively affecting benzimidazole binding efficiency. This review discusses the epidemiology of STH infections in the Philippines, the implementation of the Integrated Helminth Control Program and the potential challenges posed by benzimidazole resistance. This review highlights the need for further research to assess the occurrence of benzimidazole resistance in Philippine STH populations and to explore alternative control strategies. Understanding the mechanisms of benzimidazole resistance and developing effective countermeasures is crucial for achieving sustainable STH control and elimination in the Philippines.
Clinical Staff Perceptions of Pay-for-Performance Financial Incentives for HPV Vaccine Promotion
Authors: Rodriguez Vanessa , Brignole Kathryn , Licciardello Queen Tara , Trogdon Justin G.
Published: October 2024

The purpose was to investigate clinical staff perceptions of pay-for-performance human papillomavirus (HPV) vaccination financial incentives. In 2022, the authors conducted a national survey of clinical staff (N = 2527; response rate = 57%). Respondents were (1) certified to practice in the United States; (2) practiced as a physician, physician assistant, nurse practitioner, advanced practice nurse, registered nurse, licensed practical/vocational nurse, medical assistant, or certified nursing assistant; (3) worked in pediatrics, family medicine, or general medicine specialties; and (4) had a role in HPV vaccination for children ages 9 through 12 years. The team used ordered regressions to model whether respondents agreed with (ie, “Strongly agreed” or “Agreed” on a 5-point Likert scale) each of the 9 statements. The statements were mapped to domains based on the theory of planned behavior: attitudes (5 statements), perceived behavioral control (2), and norms (2). Favorable responses to 9 statements ranged from 32% to 85%; 5/9 items had more than 50% favorable responses. The following example odds ratios (ORs) are for “agree” versus “neutral” or “disagree” to change their behavior to obtain the incentive. Clinical staff with prior experience with incentives were more likely to agree with 8/9 positive statements about incentives (eg, OR = 1.32 [95% confidence interval {CI}: 1.12–1.57]). Family medicine clinics were more likely than pediatric clinics to agree with 5/9 statements (eg, OR = 1.42 [95% CI: 1.18–1.70]). Clinical staff with more years of experience were less likely to agree with 6/9 statements (eg, OR = 0.97 [95% CI: 0.97–0.98]). Clinical staff’s perceptions of pay-for-performance HPV vaccination financial incentives were generally favorable.
UK Government COVID-19 Response Employees’ Perceptions of Working From Home
Authors: Hall Charlotte E. , Brooks Samantha K. , Greenberg Neil , Weston Dale
Published: October 2024

Objective

This study investigates perceptions of homeworking in UK Government response-focused employees that contributed to the COVID-19 pandemic response.

Method

A cross-sectional online survey with open-ended questions was conducted. Free-text responses detailing participants’ perceptions of barriers, facilitators, advantages, and disadvantages were analyzed using content analysis.

Results

A total of 1943 free-text responses (from 150 participants) were analyzed. There were many conflicting advantages and disadvantages provided by participants, but crudely more positive statements were provided than negative. Flexibility associated with working from home was the most common positive factor, and the isolation and impact on working relationships was the most reported negative factor of working from home.

Conclusions

We suggest a ‘one size fits all’ approach to supporting staff working from home is not fit for purpose due to individual circumstances and contextual factors.
Trust and Organizational Commitment in a Postpandemic Environment
Authors: Porter Marlene T. , Williams Kate , Boaze Alicia , Rennert Melissa , Brunson Amy
Published: October 2024

OBJECTIVE

This study aimed to evaluate nurses' trust in their leader and organizational commitment, examining the relationship between these factors postpandemic and investigating if age, tenure, and specialty area predicted trust and commitment.

BACKGROUND

The nursing shortage was intensified by COVID-19. Nonnursing studies have explored the relationship of employee trust with organizational commitment, illustrating sparsity in nursing literature.

METHODS

This study used a cross-sectional, descriptive, correlational design. An electronic survey was sent to more than 1000 nurses, with a final sample size of 135 over 6 weeks.

RESULTS

Results demonstrated high levels of both trust and commitment. The correlation coefficients of all study variables were significant (P < 0.001). Organizational tenure predicted employee trust.

CONCLUSIONS

Developing leadership skills in building trust with the nursing team contributes to increased organizational commitment. Interventions such as leader development in establishing trust and building relationships with their team members may improve nurse retention and organizational commitment.
Expedited Partner Therapy Review
Authors: Jackson Kendra J. , Pickett Michelle L.
Published: October 2024

Sexually transmitted infection rates continue to rise in adolescents and young adults. Treatment of patients and their partners is vitally important to prevent reinfection and morbidity. Expedited partner therapy (EPT) is a legally available option for clinicians. EPT is endorsed by the Centers for Disease Control and Prevention and allows clinicians to prescribe medication for certain STIs for their patients' partner(s) without an evaluation of the partner(s). However, EPT is underutilized, and multisystem-level barriers exist to successful EPT exist. This article reviews the indications of EPT, common barriers to EPT and solutions to overcome these barriers, and practical considerations when prescribing EPT.
Visual Outcomes of Children With Craniosynostosis
Authors: Painter Sally L. , Wadlow Laura , Kasbekar Shivani , Rodrigues Desiderio , Wielogorska Natasha , Abbott Joseph
Published: October 2024

Craniosynostosis can impact the visual development of a child. Historically, children with craniosynostosis, particularly when associated with a syndrome, had a significant risk of vision loss. The authors aimed to study the incidence of ophthalmic pathology in a modern, multidisciplinary craniosynostosis practice. Children aged 7 to 13 years attending face-to-face ophthalmic craniofacial clinics between February 2020 and June 2021 were included in a retrospective case note review. Visual acuity, ocular alignment, optic nerve function, and retinal nerve fiber layer (RNFL) condition using optical coherence tomography (OCT) were recorded. Forty-three children (30 girls) were assessed at a median age of 10.3 years (7.8–13.1). Eleven children had unicoronal synostosis, 15 had single-suture synostosis not involving the coronal, 14 had multisuture synostosis involving the coronal, and 3 had multisuture synostosis not involving the coronal. Thirty-two out of 43 had craniofacial surgery. Sixty-seven percent required glasses. Forty-nine percent had strabismus, 11/43 (26%) had squint surgery, and 2/43 (5%) had tarsorrhaphy for corneal protection. Four out of 43 (9%) had papilloedema detected; however, at the final review, 15/68 (22%) eyes showed RNFL changes on OCT imaging, none of whom had optic atrophy. Two children did not meet UK driving standards due to refractive amblyopia; no children were registered as sight impaired. In this cohort, optic atrophy and visual loss due to exposure keratopathy were not seen. A high incidence of strabismus, glasses wear, and amblyopia is persistent. Binocular visual impairment was rare in this cohort: 95% met UK driving standards. Visual outcomes appear to be improving coinciding with improved craniofacial care alongside multidisciplinary team working.
Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4
+
decline
Authors: Baxter James , Villabona-Arenas Ch. Julián , Thompson Robin N. , Hué Stéphane , Regoes Roland R. , Kouyos Roger D. , Günthard Huldrych F. , Albert Jan , Leigh Brown Andrew , Atkins Katherine E.
Published: October 2024

HIV-1 transmission precipitates a stringent genetic bottleneck, with 75% of new infections initiated by a single genetic variant. Where multiple variants initiate infection, recipient set point viral load (SpVL) and the rate of CD4
+
T cell decline may be elevated, but these findings remain inconsistent. Here, we summarised the evidence for this phenomenon, then tested whether previous studies possessed sufficient statistical power to reliably identify a true effect of multiple variant infection leading to higher SpVL. Next, we combined models of HIV-1 transmission, heritability and disease progression to understand whether available data suggest a faster CD4
+
T cell decline would be expected to associated with multiple variant infection, without an explicit dependency between the two. First, we found that most studies had insufficient power to identify a true significant difference, prompting an explanation for previous inconsistencies. Next, our model framework revealed we would not expect to observe a positive association between multiple variant infections and faster CD4
+
T cell decline, in the absence of an explicit dependency. Consequently, while empirical evidence may be consistent with a positive association between multiple variant infection and faster CD4
+
T cell decline, further investigation is required to establish a causal basis.
Inertial coupling of the hummingbird body in the flight mechanics of an escape manoeuvre
Authors: Haque Mohammad Nasirul , Tobalske Bret W. , Cheng Bo , Luo Haoxiang
Published: October 2024

When a hovering hummingbird performs a rapid escape manoeuvre in response to a perceived threat from the front side, its body may go through simultaneous pitch, yaw and roll rotations. In this study, we examined the inertial coupling of the three-axis body rotations and its effect on the flight mechanics of the manoeuvre using analyses of high-speed videos as well as high-fidelity computational modelling of the aerodynamics and inertial forces. We found that while a bird’s pitch-up was occurring, inertial coupling between yaw and roll helped slow down and terminate the pitch, thus serving as a passive control mechanism for the manoeuvre. Furthermore, an inertial coupling between pitch-up and roll can help accelerate yaw before the roll–yaw coupling. Different from the aerodynamic mechanisms that aircraft and animal flyers typically rely on for flight control, we hypothesize that inertial coupling is a built-in mechanism in the flight mechanics of hummingbirds that helps them achieve superb aerial agility.