bluuebunny/crossref_metadata_2025 huggingface dataset:
Respiratory Isolation for Tuberculosis: A Historical Perspective
Authors: Karakousis Petros C , Mooney Graham
Published: October 2024

Although tuberculosis is an ancient disease, recognition of its airborne route of transmission, with implications for respiratory isolation, is relatively recent. Historically, the disease was believed to be hereditary or contracted by inhaling ‘miasma,’ or corrupted air, and patients were not routinely isolated. The sanatorium initially served as a place of healing for patients with tuberculosis. Discovery of the tubercle bacillus and its mode of transmission via aerosol in the late 19th/early 20th century reinforced the important public health role of sanatoria and tuberculosis hospitals in preventing disease transmission through isolation. In recent decades, outpatients receiving treatment are required to remain in respiratory isolation at home until they are deemed noninfectious based on multiple sputum samples. This historical review demonstrates that despite changing medical knowledge, drug therapies, and social conditions over time, the role of isolation remains an important topic of debate in the treatment of patients with pulmonary tuberculosis.
Reduced Red Blood Cell Deformability in Vivax Malaria
Authors: Rathnam Jeyamalar T Thurai , Grigg Matthew J , Dondorp Arjen M , William Timothy , Rajasekhar Megha , Rajahram Giri , Simpson Julie A , Barber Bridget E , Anstey Nicholas M
Published: October 2024

Reduced deformability of both infected and uninfected red blood cells (RBCs) contributes to pathogenesis in Plasmodium falciparum malaria. Whole-blood RBC deformability (RBC-D) is not well characterized in Plasmodium vivax malaria. We used a laser-assisted optical rotational cell analyzer to measure the RBC-D in fresh whole-blood samples from Malaysian patients with vivax malaria (n = 25). Deformability of whole-blood RBCs, the vast majority of which were uninfected, was reduced in vivax malaria compared with controls (n = 15), though not to the same degree as in falciparum malaria (n = 90). Reduced RBC-D may contribute to the pathogenesis of vivax malaria, including splenic retention of uninfected RBCs.
When in Debt, Appoint Women? A Re-Examination of Aid, Debt, and the Inclusion of Women in African Cabinets
Authors: Breuning Marijke , Akyol Seyma , Yun Sung Min
Published: October 2024

Are more aid-dependent and indebted countries more likely to include women in their cabinets? Several studies have suggested that such countries seek to please donors and lenders. Focusing on Africa, we test whether leaders respond to international incentives and, specifically, signal donors and lenders that they value gender equality in political decision-making. Although leaders have more direct control over the gender composition of the cabinet than the legislature, our analyses do not show that aid dependence and indebtedness result in more women in either the cabinet or the legislature. We operationalize aid dependence and indebtedness as a proportion of recipient gross national income, which we argue better reflects the aid and loan recipients’ vulnerability to external pressure. Using regression analysis techniques and multiple robustness checks to evaluate our panel data, our findings remain consistent with arguments that African states have stronger bargaining positions than the foreign aid literature has acknowledged.
Real-world effectiveness of early anti-SARS therapy in severely immunocompromised COVID-19 outpatients during the SARS-CoV-2 omicron variant era: a propensity score–adjusted retrospective cohort study
Authors: Pinargote-Celorio Héctor , Moreno-Pérez Óscar , González-De-La-Aleja Pilar , Llenas-García Jara , Martínez Pérez-Crespo Pedro María , Rodríguez-Díaz Juan-Carlos , Martínez-López Belén , Merchante Gutiérrez Nicolás , Ramos-Rincón José-Manuel , Merino Esperanza
Published: October 2024

Background

The effectiveness of the early treatment for antiviral agents in SARS-CoV-2 infection is closely related to patient comorbidities. Data on effectiveness in immunocompromised patients are limited, with reports involving highly heterogeneous and not well-defined populations. We aimed to assess the effectiveness of treatment in reducing hospitalizations in a real-world cohort of severely immunocompromised COVID-19 outpatients.

Patients and methods

We conducted a multicentre, retrospective, observational cohort study of immunocompromised outpatients attended in infectious diseases departments from 1 January to 31 December 2022. Propensity score matching (PSM) multivariable logistic regression models were used to estimate the adjusted odds ratio [(aOR, 95% confidence interval (CI)] for the association between antiviral prescription and outcome (COVID-19–related hospitalization up to Day 90).

Results

We identified 746 immunocompromised outpatients with confirmed SARS-CoV-2 infection. After eligibility criteria and PSM, a total of 410 patients were analysed: 205 receiving treatment (remdesivir, sotrovimab or nirmatrelvir/ritonavir) and 205 matched controls. Fifty-two patients required at least one COVID-19–related hospitalization 8 (3.9%) versus 44 (21.5%) in the antiviral and matched control cohorts, respectively. There were 13 deaths at 90 days, of which only 4 were COVID-19–related and none in the antiviral treatment group. After adjustment for residual confounders, the use of early therapy was associated with a protective effect on the risk of hospitalization [aOR 0.13 (0.05–0.29)], as was the use of biological immunomodulators [aOR 0.27 (0.10–0.74)], whereas chronic obstructive pulmonary disease [aOR 4.65 (1.09–19.69)] and anti-CD20 use [aOR 2.76 (1.31–5.81)] increased the odds.

Conclusions

Early antiviral treatment was associated with a reduced risk of COVID-19–related hospitalization in ambulatory severely immunocompromised COVID-19 patients.
Target-site cefiderocol pharmacokinetics in soft tissues of healthy volunteers
Authors: Sanz-Codina Maria , van Os Wisse , Pham Anh Duc , Jorda Anselm , Wölf-Duchek Michael , Bergmann Felix , Lackner Edith , Lier Constantin , van Hasselt J G Coen , Minichmayr Iris K , Dorn Christoph , Zeitlinger Markus , al Jalali Valentin
Published: October 2024

Background

Cefiderocol may potentially be used to treat skin and soft tissue infections (SSTIs). However, the pharmacokinetics of cefiderocol in human soft tissues have not yet been determined. The objective of the present PK study was to investigate whether target-site concentrations of cefiderocol are sufficiently high for the treatment of SSTIs.

Methods

In this pharmacokinetic study, a single intravenous dose of 2 g cefiderocol was administered to eight healthy male volunteers. Drug concentrations were determined in plasma, muscle and subcutis over 8 h. Free plasma concentrations were calculated using the plasma protein binding determined with ultrafiltration. Free tissue concentrations were obtained using microdialysis. Penetration ratios were calculated as AUC0-8h_free_tissue/AUC0-8h_free_plasma. A population pharmacokinetic model was developed, and the probability of target attainment (PTA) was determined using Monte Carlo simulations.

Results

Cefiderocol showed good tissue penetration, with mean penetration ratios ± standard deviation of 0.99 ± 0.33 and 0.92 ± 0.30 for subcutis and muscle, respectively. Cefiderocol pharmacokinetics in plasma were best described with a two-compartment model, and tissue concentrations were described by scaling the tissue concentrations to concentrations in the peripheral compartment of the plasma model. For a thrice-daily regimen with 2 g doses intravenously infused over 3 h, PTA was ≥90% for MIC values up to 4 mg/L, both based on free plasma and soft tissue pharmacokinetics.

Conclusions

This study indicates that a dose of 2 g cefiderocol achieves concentrations in plasma considered sufficient for treating relevant bacterial species. Assuming a comparable PK/PD target for soft tissues, sufficiently high concentrations would also be achieved in soft tissues.
High-fat and high-sugar diets induce rapid adaptations of fat storage in the house fly Musca domestica L.
Authors: Boatta Francesco , van Hal Jurgen , Beukeboom Leo W , Ellers Jacintha
Published: October 2024

Dietary change can be a strong evolutionary force and lead to rapid adaptation in organisms. High-fat and high-sugar diets can challenge key metabolic pathways, negatively affecting other life history traits and inducing pathologies such as obesity and diabetes. In this study, we use experimental evolution to investigate the plastic and evolutionary responses to nutritionally unbalanced diets. We reared replicated lines of larvae of the housefly Musca domestica on a fat-enriched (FAT), a sugar-enriched (SUG), and a control (CTRL) diet for thirteen generations. We measured development time in each generation and larval growth and fat accumulation in generations 1, 7, and 13. Subsequently, all lines were reared for one generation on the control diet to detect any plastic and evolutionary changes. In the first generation, time to pupation decreased on a fat-rich diet and increased on a sugar-rich diet. The fat-rich diet increased fat accumulation and, to a lesser extent, the dry weight of the larvae. Multigenerational exposure to unbalanced diets caused compensatory changes in development time, dry weight, and absolute and relative fat content, although pattern and timing depended on diet and trait. When put back on a control diet, many of the changes induced by the unbalanced diets disappeared, indicating that the diet has large plastic effects. Nevertheless, fat-evolved lines still grew significantly larger than the sugar-evolved lines, and sugar-evolved lines had consistently lower fat content. This can be an effect of parental diet or an evolutionary change in nutrient metabolism as a consequence of multigenerational exposure to unbalanced diets.
The conservation value of small population remnants: Variability in inbreeding depression and heterosis of a perennial herb, the narrow-leaved purple coneflower (Echinacea angustifolia)
Authors: Thoen Riley D , Southgate Andrea , Kiefer Gretel , Shaw Ruth G , Wagenius Stuart
Published: October 2024

Anthropogenically fragmented populations may have reduced fitness due to loss of genetic diversity and inbreeding. The extent of such fitness losses due to fragmentation and potential gains from conservation actions are infrequently assessed together empirically. Controlled crosses within and among populations can identify whether populations are at risk of inbreeding depression and whether inter-population crossing alleviates fitness loss. Because fitness depends on the environment and life stage, studies quantifying cumulative fitness over a large portion of the lifecycle in conditions that mimic natural environments are most informative. To assess the fitness consequences of habitat fragmentation, we leveraged controlled within-family, within-population, and between-population crosses to quantify inbreeding depression and heterosis in seven populations of Echinacea angustifolia within a 6,400-ha area. We then assessed cumulative offspring fitness after 14 yr of growth in a natural experimental plot (N = 1,136). The mean fitness of progeny from within-population crosses varied considerably, indicating genetic differentiation among source populations, even though these sites are all less than 9 km apart. The fitness consequences of within-family and between-population crosses varied in magnitude and direction. Only one of the seven populations showed inbreeding depression of high effect, while four populations showed substantial heterosis. Outbreeding depression was rare and slight. Our findings indicate that local crossings between isolated populations yield unpredictable fitness consequences ranging from slight decreases to substantial increases. Interestingly, inbreeding depression and heterosis did not relate closely to population size, suggesting that all fragmented populations could contribute to conservation goals as either pollen recipients or donors.
Prognostic risk score and index including the platelet-to-lymphocyte ratio and lactate dehydrogenase in patients with metastatic or unresectable urothelial carcinoma treated with immune checkpoint inhibitors
Authors: Kobayashi Keita , Sakano Shigeru , Matsumoto Hiroaki , Yamamoto Mitsutaka , Tsuchida Masahiro , Tei Yasuhide , Nagao Kazuhiro , Oba Kazuo , Kitahara Seiji , Yano Seiji , Yoshihiro Satoru , Yamamoto Yoshiaki , Ohmi Chietaka , Komatsu Hirotaka , Misumi Taku , Akao Jumpei , Shiraishi Koji
Published: October 2024

Background

Avelumab and pembrolizumab are administered after platinum-based chemotherapy for the treatment of metastatic urothelial carcinoma. We explored the prognostic factors and risk scores for predicting the outcomes of metastatic or unresectable urothelial carcinoma at the start of treatment with immune checkpoint inhibitors.

Methods

This retrospective study included patients with metastatic or unresectable urothelial carcinoma treated with avelumab or pembrolizumab after platinum-based chemotherapy between January 2017 and December 2022. Prognostic factors, including patient and tumor characteristics and blood data at the initiation of immune checkpoint inhibitor therapy, were examined.

Results

This study included 36 and 207 patients treated with avelumab and pembrolizumab, respectively, for metastatic or unresectable urothelial carcinoma. Eastern Cooperative Oncology Group performance status, presence of visceral metastases, platelet-to-lymphocyte ratio and lactate dehydrogenase levels were independent prognostic factors for predicting overall survival. The median overall survival of patients in the risk-score model was 58.5 months (score zero), 27.9 months (one), 13.1 months (two) and 3.9 months (three or higher). The C-index for overall survival was 0.718 for the newly developed risk score compared with 0.679 for the Bellmunt score and 0.703 for the Bellmunt-C-reactive protein score. Additionally, the C-index for overall survival using the immune prognostic index derived from lactate dehydrogenase and the platelet-to-lymphocyte ratio was 0.646 compared with 0.615 for the Lung Immune Prognostic Index.

Conclusions

A risk score that includes the platelet-to-lymphocyte ratio and lactate dehydrogenase may serve as a useful model for predicting prognosis following the initiation of immune checkpoint inhibitors in patients with metastatic or unresectable urothelial carcinoma.
Evaluation of the In2care Mosquito Station against Culex quinquefasciatus mosquitoes (Diptera: Culicidae) under semifield conditions
Authors: Buckner Eva A , Romero-Weaver Ana L , Schluep Sierra M , Bellamy Shawna K , Zimler Rebecca A , Kendziorski Natalie L , Ramirez Daviela , Whitehead Shelley A
Published: October 2024

Culex quinquefasciatus is an important mosquito vector responsible for the transmission of filarial worms, arthropod-borne viruses like Oropouche, St. Louis encephalitis, and West Nile and protozoans that cause avian malaria. Due to insecticide resistance documented in Cx. quinquefasciatus populations worldwide, integrated vector management programs can benefit from new strategies to control this species. The In2Care Mosquito Station (In2Care station), a commercially available dissemination station containing pyriproxyfen (PPF) and Beauveria bassiana spores, has been shown to be effective against skip-ovipositing Aedes aegypti and Aedes albopictus in previously conducted semifield and field trials. To determine the potential of Cx. quinquefasciatus adult females to autodisseminate PPF and if the In2Care station could be used for Cx. quinquefasciatus control, we assessed its efficacy in a semifield setting against wild Cx. quinquefasciatus. We found that the In2Care station was attractive to gravid Cx. quinquefasciatus females, with a significantly higher percentage of egg rafts laid in the In2Care station compared to alternative ovipots. Adult females successfully autodisseminated PPF from the In2Care station to surrounding ovipots, leading to a significant increase in mosquito emergence inhibition. Additionally, adult Cx. quinquefasciatus exposure to B. bassiana spores significantly reduced mosquito survivorship. These results suggest that the In2Care station may be effective against Cx. quinquefasciatus in addition to Ae. aegypti and Ae. albopictus. Additional field evaluations are needed to assess impacts at the population level.
Procedural politicking for what? Bureaucratic reputation and democratic governance
Authors: Park Joohyung
Published: October 2024

As the bureaucratic policymaking process has frequently deviated from conventional procedures contemplated by administrative law statutes, recent research suggests that bureaucrats strategically use rulemaking procedures to pursue their own goals and circumvent political interventions. However, the literature has often neglected implementation issues that bureaucrats confront in the policymaking process. Building on a bureaucratic reputation perspective that explicitly recognizes bureaucrats’ concern for implementation failure and reputational damage, this study examines when and why U.S. federal agencies issue rules without prior notice and comment instead of proposing rules through the conventional notice-and-comment process. Using logistic regressions with fixed effects, based on over 16,000 rules published between 2000 and 2020, we find that agencies are more likely to solicit prior public comment when making more complex and stringent rules. However, they tend to bypass it when making new rules and joint rules with other agencies. This study also shows that the positive effect of rule stringency on agencies’ use of the conventional notice-and-comment process tends to be more pronounced in agencies with higher proportions of professional bureaucrats. Overall, our findings indicate that bureaucrats’ choices of rulemaking procedures might be shaped by their incentives to prevent implementation failure and preserve agency reputation, which can be compatible with the norms of democratic governance.
Effect of neutron beam properties on dose distributions in a water phantom for boron neutron capture therapy
Authors: Ishikawa Akihisa , Tanaka Hiroki , Nakamura Satoshi , Kumada Hiroaki , Sakurai Yoshinori , Watanabe Kenichi , Yoshihashi Sachiko , Tanagami Yuki , Uritani Akira , Kiyanagi Yoshiaki
Published: October 2024

From the viewpoints of the advantage depths (ADs), peak tumor dose and skin dose, we evaluated the effect on the dose distribution of neutron beam properties, namely the ratio between thermal and epithermal neutron fluxes (thermal/epithermal ratio), fast neutron component and γ-ray component. Several parameter surveys were conducted with respect to the beam properties of neutron sources for boron neutron capture therapy assuming boronophenylalanine as the boron agent using our dose calculation tool, called SiDE. The ADs decreased by 3% at a thermal/epithermal ratio of 20–30% compared with the current recommendation of 5%. The skin dose increased with the increasing thermal/epithermal ratio, reaching a restricted value of 14 Gyeq at a thermal/epithermal ratio of 48%. The fast neutron component was modified using two different models, namely the ‘linear model’, in which the fast neutron intensity decreases log-linearly with the increasing neutron energy, and the ‘moderator thickness (MT) model’, in which the fast neutron component is varied by adjusting the MT in a virtual beam shaping assembly. Although a higher fast neutron component indicated a higher skin dose, the increment was <10% at a fast neutron component of <1 × 10−12 Gy cm2 for both models. Furthermore, in the MT model, the epithermal neutron intensity at a fast neutron component of 6.8 × 10−13 Gy cm2 was 41% higher compared with that of 2 × 10−13 Gy cm2. The γ-ray component also caused no significant disadvantages up to several times larger compared with the current recommendation.
Forecasting school enrollments in the Australian Capital Territory
Authors: Shen Tianyu , Raymer James , Hendy Caroline
Published: October 2024

School enrollment forecasts are vital for effective planning. This study introduces a probabilistic multiregional population projection model, which accounts for different components, including preschool entries, migration, grade progression, and graduations. Using different distributions with a cohort component projection and Monte Carlo simulation, this paper forecasts student enrollments for each school and academic year level in the Australian Capital Territory based on the annual record-level administrative data. In the in-sample validation tests, the model’s overall performance is robust, and the probabilistic design offers reliable prediction intervals reflecting the variation in observed values. The paper ends with a discussion on the importance of prediction intervals for informing school planning.
A case of minimum invasive debranch thoracic endovascular aortic repair for isolated left vertebral artery: complete revascularization without artificial vessels via a single small incision
Authors: Tsutsui Masahiro , Miyatani Kazuki , Shirakura Kentaro , Setogawa Yuki , Suzuki Fumitaka , Miyamoto Hiroyuki , Okubo Ryo , Ushioda Ryohei , Kunioka Shingo , Ishikawa Natsuya , Otani Norihumi , Kamiya Hiroyuki
Published: October 2024

Isolated left vertebral artery (ILVA) is one of the most frequent vertebral abnormalities. When performing thoracic endovascular aortic repair (TEVAR), the ILVA may have to be closed depending on the position of the stent graft; in these cases, the decision to reconstruct the ILVA depends on the state of cerebral blood flow. Here, we report a case of a 68-year-old male, in whom the Willis arterial circle was incomplete; we therefore performed a reconstructive method during zone 2-landing TEVAR that ensured ILVA and left subclavian artery blood flow without the use of artificial vessels. Only one supraclavicular incision was required for reconstruction. This method has some procedural difficulties; however, it does not use artificial blood vessels and can be performed with a single incision.
Mixed neuroendocrine–nonneuroendocrine epithelial neoplasm of muscle invasive bladder cancer: a clinicopathologic case study
Authors: Tran Pierre , Rama Sai P , Prasad Chaya , Do Hanh , Parsa Cyrus
Published: October 2024

Mixed neuroendocrine–nonneuroendocrine epithelial neoplasms are rare malignant neoplasms that may occur in the bladder with highly aggressive behavior. Because of its worse prognosis, when compared to the pure urothelial carcinoma without the neuroendocrine component, the bladder mixed neuroendocrine–nonneuroendocrine epithelial neoplasm may be considered a distinct clinicopathologic entity. We present a case of mixed neuroendocrine–nonneuroendocrine epithelial neoplasm occurring in the urinary bladder of an elderly female with a personal history of chronic kidney disease, drug-resistant urinary tract infections, and neurogenic bladder. Her presenting symptoms included complaints of abdominal pain, urinary urgency, oliguria, dysuria, and occasional hematuria. Recognition of the clinicopathologic features of these rare aggressive neoplasms is important for accurate early diagnosis, necessitating appropriate therapeutic management.
Appendicular diverticulosis complicated by acute appendicitis and organizing abscess: what does the surgeon need to consider intraoperatively?
Authors: Al Jabran Hussain , Aljawad Hameed , Alnajjar Jawad S , AlRaihan Jawaher , Al Omar Sarah
Published: October 2024

Acute appendicitis is a common surgical emergency, affecting 7%–10% of people worldwide, whereas appendicular diverticulosis is rare, occurring in 0.004%–2.1% of appendectomy cases and often mimicking appendicitis symptoms. A 35-year-old male presented with right lower quadrant pain, nausea, vomiting, and diarrhea. Clinical examination showed tenderness in the right iliac fossa. Imaging suggested uncomplicated acute appendicitis, but surgery revealed an appendiceal mass suspected to be a carcinoid tumor. Histopathology post-appendectomy diagnosed appendicular diverticulosis complicated by acute appendicitis. This case emphasizes the need for thorough histopathological examination in appendectomy cases to accurately diagnose and differentiate appendicular conditions. Appendiceal diverticulitis should be considered in the differential diagnosis of right lower quadrant pain to ensure proper surgical intervention and prevent complications.
Follow-up report on pulmonary mucosa-associated lymphoma in a patient with von Hippel–Lindau disease
Authors: Olarewaju Bukola A , Tejon Judy B , Osundiji Mayowa A
Published: October 2024

With the increasing opportunities for medical management of von Hippel–Lindau (VHL)-related lesions, fundamental questions are arising regarding the possibilities of the FDA-approved medication (Belzutifan) to delay the progression of other non-VHL-related tumors that are not requiring urgent surgical interventions. We present a follow-up report on a VHL patient, with a co-morbid history of pulmonary mucosa-associated lymphoid tissue lymphoma, who was initially described in the clinical scientific literature ~10 years ago. This patient’s case highlights some of the challenges for some VHL patients with comorbid non-VHL-related tumors and potential opportunities for targeted support.
‘Ed: Agberowe’, Seventeenth-Century Collector of Restoration Playbooks
Authors: McInnis David
Published: October 2024

A number of seventeenth-century books-almost exclusively Restoration playbooks-bear the ownership inscription ‘Ed: Agberowe’ on their title pages (and often a second signature on a subsequent page). This article provides an overview of the books known to have been in Agberowe’s collection and supplies a brief biographical sketch, revealing some impressive literary connections to Butler, Milton, and Marvell. Recovery of Agberowe’s life and library has intrinsic interest in terms of his colourful biography and his literary tastes, which, it is suggested, may have developed in relation to his employment throughout the 1660s and via the family of his wife, Theophila Cornewall. Perhaps more significant, though, is that the recovery of Agberowe’s story provides a new example of a seventeenth-century book-collector who seems to have been interested primarily in acquiring playbooks.
REBELS-25: discovery of a dynamically cold disc galaxy at z = 7.31
Authors: Rowland Lucie E , Hodge Jacqueline , Bouwens Rychard , Piña Pavel E Mancera , Hygate Alexander , Algera Hiddo , Aravena Manuel , Bowler Rebecca , da Cunha Elisabete , Dayal Pratika , Ferrara Andrea , Herard-Demanche Thomas , Inami Hanae , van Leeuwen Ivana , de Looze Ilse , Oesch Pascal , Pallottini Andrea , Phillips Siân , Rybak Matus , Schouws Sander , Smit Renske , Sommovigo Laura , Stefanon Mauro , van der Werf Paul
Published: October 2024

We present high-resolution ($\sim 0.14$ arcsec = 710 pc) Atacama Large Millimetre/submillimetre Array [C ii] 158 $\mu$m and dust continuum follow-up observations of REBELS-25, a [C ii]-luminous ($L_{\mathrm{[CII]}}=(1.7\pm 0.2)\times 10^9\, \mathrm{L_{\odot }}$) galaxy at redshift $z=7.3065\pm 0.0001$. These high-resolution, high signal-to-noise observations allow us to study the sub-kpc morphology and kinematics of this massive ($M_* = 8^{+4}_{-2} \times 10^9 \mathrm{{\rm M}_{\odot }}$) star-forming (SFR$_{\mathrm{UV+IR}} = 199^{+101}_{-63} \mathrm{{\rm M}_{\odot }} \mathrm{yr}^{-1}$) galaxy in the Epoch of Reionization. By modelling the kinematics with $^{\mathrm{3D}}$BAROLO, we find it has a low-velocity dispersion ($\bar{\sigma } = 33^{+9}_{-7}$ km s$^{-1}$) and a high ratio of ordered-to-random motion ($V_{\mathrm{rot, ~max}}/\bar{\sigma } = 11 ^{+6}_{-5}$), indicating that REBELS-25 is a dynamically cold disc. Additionally, we find that the [C ii] distribution is well fit by a near-exponential disc model, with a Sérsic index, n, of $1.3 \pm 0.2$, and we see tentative evidence of more complex non-axisymmetric structures suggestive of a bar in the [C ii] and dust continuum emission. By comparing to other high spatial resolution cold gas kinematic studies, we find that dynamically cold discs seem to be more common in the high-redshift Universe than expected based on prevailing galaxy formation theories, which typically predict more turbulent and dispersion-dominated galaxies in the early Universe as an outcome of merger activity, gas accretion, and more intense feedback. This higher degree of rotational support seems instead to be consistent with recent cosmological simulations that have highlighted the contrast between cold and warm ionized gas tracers, particularly for massive galaxies. We therefore show that dynamically settled disc galaxies can form as early as 700 Myr after the big bang
An added value of azithromycin: mitigation of doxorubicin-associated oxidative damage and genotoxicity in normal human bronchial epithelium cells
Authors: Shokrzadeh Shaghayegh , Moghim Shahrzad , Shokrzadeh Mohammad , Aghajanshakeri Shaghayegh
Published: October 2024

Doxorubicin, a well-known and widely used antineoplastic agent with direct ROS-accumulating activity, has proven effective in treating various cancer types. However, its non-specific cytotoxicity towards non-cancerous cells prompts concerns regarding potential adverse effects. Azithromycin is an antibiotic for treating bacterial infections and an anti-inflammatory agent, particularly beneficial in managing respiratory conditions like bronchitis and sinusitis. Despite azithromycin’s well-documented antibacterial properties, its potential cellular/genomic protective effects remain unexplored. As an in vitro model, BEAS-2B cells (normal human bronchial epithelium cells) were employed in this study to assess whether azithromycin possesses any protective properties against doxorubicin-induced cellular toxicity. Cells in pretreatment culture were treated to various amounts of azithromycin (3.125, 6.25, 12.5, 25, and 50 μg/ml) in combination with doxorubicin at IC50 (0.08 μg/ml). Doxorubicin at 0.08 μg/ml highlighted cytotoxicity, oxidative stress, and genotoxicity. Azithromycin at 25 and 50 μg/ml markedly modulated oxidative stress and genomic damage by decreasing the ROS and LPO amounts and suppressing DNA fragmentation in the comet assay parameters. Consequently, azithromycin may be regarded as a cytomodulating, antigenotoxic, and antioxidant agent.
SubCELL: the landscape of subcellular compartment-specific molecular interactions
Authors: Zhang Yintao , Jiang Wanghao , Li Teng , Xu Hangwei , Zhu Yimiao , Fang Kerui , Ren Xinyu , Wang Shanshan , Chen Yuzong , Zhou Ying , Zhu Feng
Published: October 2024

The subcellular compartment-specific molecular interactions (SCSIs) are the building blocks for most molecular functions, biological processes and disease pathogeneses. Extensive experiments have therefore been conducted to accumulate the valuable information of SCSIs, but none of the available databases has been constructed to describe those data. In this study, a novel knowledge base SubCELL is thus introduced to depict the landscape of SCSIs among DNAs/RNAs/proteins. This database is UNIQUE in (a) providing, for the first time, the experimentally-identified SCSIs, (b) systematically illustrating a large number of SCSIs inferred based on well-established method and (c) collecting experimentally-determined subcellular locations for the DNAs/RNAs/proteins of diverse species. Given the essential physiological/pathological role of SCSIs, the SubCELL is highly expected to have great implications for modern molecular biological study, which can be freely accessed with no login requirement at: https://idrblab.org/subcell/.
Posttraumatic Pseudomonas aeruginosa Osteomyelitis in Mosul and Gaza: A Retrospective Cohort Study, 2018–2022
Authors: Taher Ali Qasim Mohammad , Aqel Rasha , Alnajjar Mohammed , Walker Caroline , Repetto Ernestina , Raad Marwah , Gomez Fabiola Gordillo , Nyaruhirira Innocent , Michel Justine , Herard Patrick , Kanapathipillai Rupa , Moussally Krystel , Khalife Mohamad
Published: October 2024

Background

The history of conflicts in the Middle East has resulted in a high burden of complications from conflict-related wounds like posttraumatic osteomyelitis (PTO). This is particularly challenging to manage in settings like Mosul, Iraq and Gaza, Palestine, where healthcare systems are weakened. In nonconflict settings, PTO caused by Pseudomonas aeruginosa (PAPTO) can lead to >20% of treatment failures. We aim to describe the clinical characteristics, outcomes, and management, in PAPTO patients admitted to Médecins Sans Frontières (MSF) facilities in Mosul and Gaza between 1 April 2018 and 31 January 2022.

Methods

We conducted a retrospective cohort study on patients with PAPTO diagnosed with culture of intraoperative bone biopsy, using routinely collected data.

Results

Among 66 PAPTO episodes from 61 enrolled patients, 37.9% had a multidrug-resistant Pseudomonas aeruginosa, with higher antibiotic resistance in Gaza. Polymicrobial infections were prevalent (74.2%), mainly involving Staphylococcus aureus (74.1%), being predominantly methicillin-resistant (95.0%). Overall, 81.7% received appropriate antibiotic treatment, with monotherapy used in 60.6% of episodes and a median treatment duration of 45.5 days. Recurrence was observed in 24.6% of episodes within a median of 195 days (interquartile range, 64–440 days). No significant differences were found in recurrence rates based on the type of antibiotic treatment (mono- or dual therapy) or episode (mono- or polymicrobial).

Conclusions

Management of PAPTO in the conflict-affected, low-resource settings of Mosul and Gaza achieved a recurrence rate aligned with global reports through appropriate and targeted antibiotic use, primarily in monotherapy, provided over a mean treatment duration of 45.5 days.
Severe Acute Respiratory Syndrome Coronavirus 2 Household Transmission During the Omicron Era in Massachusetts: A Prospective, Case-Ascertained Study Using Genomic Epidemiology
Authors: Banga Jaspreet , Brock-Fisher Taylor , Petros Brittany A , Dai Eric Y , Leonelli Ariana T , Dobbins Sabrina T , Messer Katelyn S , Nathanson Audrey B , Capone Amelia , Littlehale Nancy , Appiah-Danquah Viola , Dim Siang , Moreno Gage K , Crowther Maura , DeRuff Katherine C , MacInnis Bronwyn L , Springer Michael , Sabeti Pardis C , Stephenson Kathryn E
Published: October 2024

Background

Households are a major setting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, but there remains a lack of knowledge regarding the dynamics of viral transmission, particularly in the setting of preexisting SARS-CoV-2 immunity and evolving variants.

Methods

We conducted a prospective, case-ascertained household transmission study in the greater Boston area in March–July 2022. Anterior nasal swabs, along with clinical and demographic data, were collected for 14 days. Nasal swabs were tested for SARS-CoV-2 by polymerase chain reaction (PCR). Whole genome sequencing was performed on high-titer samples.

Results

We enrolled 33 households in a primary analysis set, with a median participant age of 25 years (range, 2–66 years), 98% of whom had received at least 2 doses of a coronavirus disease 2019 (COVID-19) vaccine. Fifty-eight percent of households had a secondary case during follow-up and the secondary attack rate (SAR) for contacts was 39%. We further examined a strict analysis set of 21 households that had only 1 PCR-positive case at baseline, finding an SAR of 22.5%. Genomic epidemiology further determined that there were multiple sources of infection for household contacts, including the index case and outside introductions. When limiting estimates to only highly probable transmissions given epidemiologic and genomic data, the SAR was 18.4%.

Conclusions

Household contacts of a person newly diagnosed with COVID-19 are at high risk for SARS-CoV-2 infection in the following 2 weeks. This is, however, not only due to infection from the household index case, but also because the presence of an infected household member implies increased SARS-CoV-2 community transmission.
Maize stigmas react differently to self- and cross-pollination and fungal invasion
Authors: Begcy Kevin , Mondragón-Palomino Mariana , Zhou Liang-Zi , Seitz Patricia-Lena , Márton Mihaela-Luiza , Dresselhaus Thomas
Published: October 2024

During sexual reproduction in flowering plants, tip-growing pollen tubes travel from the stigma inside the maternal tissues of the pistil toward ovules. In maize (Zea mays L.), the stigma is highly elongated, forming thread-like strands known as silks. Only compatible pollen tubes successfully penetrate and grow through the transmitting tract of the silk to reach the ovules. Like pollen, fungal spores germinate at the surface of silks and generate tube-like structures (hyphae) penetrating silk tissue. To elucidate commonalities and differences between silk responses to these distinctive invading cells, we compared growth behavior of the various invaders as well as the silk transcriptome after self-pollination, cross-pollination, and infection using 2 different fungi. We report that self-pollination triggers mainly senescence genes, whereas incompatible pollen from Tripsacum dactyloides leads to downregulation of rehydration, microtubule, and cell wall–related genes, explaining the slower pollen tube growth and arrest. Invasion by the ascomycete Fusarium graminearum triggers numerous defense responses including the activation of monolignol biosynthesis and NAC as well as WRKY transcription factor genes, whereas responses to the basidiomycete Ustilago maydis are generally much weaker. We present evidence that incompatible pollination and fungal infection trigger transcriptional reprograming of maize silks cell wall. Pathogen invasion also activates the phytoalexin biosynthesis pathway.
Quantifying the uniqueness and divisiveness of presidential discourse
Authors: Zhou Karen , Meitus Alexander A , Chase Milo , Wang Grace , Mykland Anne , Howell William , Tan Chenhao
Published: October 2024

Do American presidents speak discernibly different from each other? If so, in what ways? And are these differences confined to any single medium of communication? To investigate these questions, this paper introduces a novel metric of uniqueness based on large language models, develops a new lexicon for divisive speech, and presents a framework for assessing the distinctive ways in which presidents speak about their political opponents. Applying these tools to a variety of corpora of presidential speeches, we find considerable evidence that Donald Trump’s speech patterns diverge from those of all major party nominees for the presidency in recent history. Trump is significantly more distinctive than his fellow Republicans, whose uniqueness values appear closer to those of the Democrats. Contributing to these differences is Trump’s employment of divisive and antagonistic language, particularly when targeting his political opponents. These differences hold across a variety of measurement strategies, arise on both the campaign trail and in official presidential addresses, and do not appear to be an artifact of secular changes in presidential communications.
The role and mechanism of CRISPLD2 in skin fibrosis of systemic sclerosis
Authors: Ding Liqing , Bao Ding , Dai Bingying , Meng Qiming , Lv Chunliu , Luo Hui , Zhu Honglin
Published: October 2024

Objectives

SSc is an autoimmune connective tissue disease involving multiple organs. The most common clinical symptom of SSc is progressive fibrosis of the skin, and the pathologically manifestations of skin were activation and proliferation of fibroblasts and continuous proliferation of extracellular matrix. TGF-β can promote the proliferation and activation of fibroblasts, causing excessive deposition of collagen and structural proteins. Therefore, exploring the specific mechanism of TGF-β-related pathway on fibrosis is of great significance for improving skin fibrosis in SSc.

Methods

Genes related to TGF-β pathway were screened through bioinformatics analysis, and SSc phenotypes were verified in vivo and in vitro. The relevant molecular mechanisms were preliminarily discussed in combination with transcriptome sequencing.

Results

Human cysteine-rich secreted protein LCCL domain protein 2 (CRISPLD2) was found increased reactivity in TGF-β-induced fibroblasts, and the expression of ACTA2 (ɑ-SMA) decreased significantly in TGF-β-mediated fibroblasts with up-regulation of CRISPLD2.

Conclusion

CRISPLD2 was found to have increased reactivity in TGF-β-induced fibroblasts, and we further confirmed that CRISPLD2 can participate in TGF-β-induced fibroblast fibrosis from multiple perspectives and levels in negative feedback regulation, and investigated the mechanism of CRISPLD2 in fibrosis.
Proteomic analysis of toxic effects of short-term cadmium exposure on goat livers
Authors: Liu Guangyang , Shen Xiaoyun , Li Yuanfeng
Published: October 2024

Food safety is closely related to environmental pollution. It is worth noting that the long-term accumulation of Cd, a toxic heavy metal, in animals may pose a threat to human health through food chain. Previous studies have found that Cd exposure may cause liver metabolic disorders of black goats, but the mechanism of its impact on liver proteome of goats has not been widely studied. Therefore, in this study, ten male goats (Nubian black goat × native black goat) were exposed to Cd via drinking water containing CdCl2 (20 mg Cd·kg − 1·BW) for 30 days (five male goats per group). Blood physiology and liver antioxidant indices in black goats were determined and differentially expressed proteins (DEPs) in the livers of Cd-exposed goats were profiled by using TMT-labelled proteomics. It was found that plasma Hb and RBC levels as well as PCV values were decreased, liver SOD, GSH-Px, T-AOC and CAT levels were decreased, and MDA level was increased in Cd-treated goats, and 630 DEPs (up 326, down 304) in the livers of Cd-treated goats. Proteomics analysis revealed that Cd exposure affected glutathione metabolism and drug metabolism-cytochrome P450. We identified GP×2, GSTM3, and TBXAS1 as potential protein markers of early Cd toxicity in goats. This study provided theoretical basis for early diagnosis of Cd poisoning in goats.
Repeated radon exposure induced ATM kinase-mediated DNA damage response and protective autophagy in mice and human bronchial epithelial cells
Authors: Chen Xiaoyu , Shan Shan , Wang Aiqing , Tu Cheng , Wan Jianmei , Hong Chengjiao , Li Xiaohan , Wang Xueying , Yin Jieyun , Tong Jian , Tian Hailin , Xin Lili
Published: October 2024

Objective: Radon (222Rn) is a naturally occurring radioactive gas that has been closely linked with the development of lung cancer. In this study, we investigated the radon-induced DNA strand breaks, a critical event in lung carcinogenesis, and the corresponding DNA damage response (DDR) in mice and human bronchial epithelial (BEAS-2B) cells. Methods: Biomarkers of DNA double-strand breaks (DSBs), DNA repair response to DSBs, ataxia-telangiectasia mutated (ATM) kinase, autophagy, and a cell apoptosis signaling pathway as well as cell-cycle arrest and the rate of apoptosis were determined in mouse lung and BEAS-2B cells after radon exposure. Results: Repeated radon exposure induced DSBs indicated by the increasing expressions of γ-Histone 2AX (H2AX) protein and H2AX gene in a time and dose-dependent manner. Additionally, a panel of ATM-dependent repair cascades [i.e. non-homologous DNA end joining (NHEJ), cell-cycle arrest and the p38 mitogen activated protein kinase (p38MAPK)/Bax apoptosis signaling pathway] as well as the autophagy process were activated. Inhibition of autophagy by 3-methyladenine pre-treatment partially reversed the expression of NHEJ-related genes induced by radon exposure in BEAS-2B cells. Conclusions: The findings demonstrated that long-term exposure to radon gas induced DNA lesions in the form of DSBs and a series of ATM-dependent DDR pathways. Activation of the ATM-mediated autophagy may provide a protective and pro-survival effect on radon-induced DSBs.
Relationship Between the Distribution of the Pinewood Nematode (Bursaphelenchus xylophilus) and the Development of Xylem Embolism in the Stems of Japanese Black Pine (Pinus thunbergii) Seedlings Monitored by Magnetic Resonance Imaging
Authors: Akami Ai , Fukuda Kenji
Published: October 2024

The development of xylem embolism in 1-year-old stems of Japanese black pine ( Pinus thunbergii) seedlings was monitored by compact magnetic resonance imaging (MRI) after inoculation with the pinewood nematode ( Bursaphelenchus xylophilus). In parallel, the nematode distribution and population structure in the stems were examined by isolating the nematodes using the Baermann funnel technique. The vertical length and volume of massive embolisms in each seedling were strongly correlated with the maximum relative embolized area (REA) in stem cross-sections. Embolism development and nematode reproduction were not restricted to the inoculation site, as any portion of the stem could be the initial point of a population burst. The nematode population in the stem xylem was strongly correlated with the REA and with the circumferential proportion of cambial death in cross-sections monitored by MRI. The proportion of second-stage juveniles was also correlated with the REA in the xylem. In contrast, the nematode population in bark tissue was not correlated with either the REA or cambial death. These results suggested that nematode reproduction in the cambial zone is the key step in pine wilt disease, and second-stage juveniles were suggested to induce massive embolisms in the advanced stage of the disease.
IL‐17A‐neutralizing antibody ameliorates inflammation and fibrosis in rosacea by antagonizing the CXCL5/CXCR2 axis
Authors: Zhang Chuanxi , Jin Hui , Kang Yumeng , Wu Yiling , Zheng Ruiping , Zhang Ziyan , Xu Hong , Cai Wenchen , Gao Xuemin , Liu Heliang , Mao Na , Yang Jie
Published: October 2024

Rosacea is a chronic inflammatory skin disorder that can lead to fibrosis. However, the mechanisms underlying fibrosis in the later stages of rosacea have been less thoroughly investigated. Interleukin‐17A (IL‐17A) has been implicated in both inflammation and organ fibrosis; however, the effectiveness and mechanism of IL‐17A‐neutralizing antibodies in the later stages of rosacea‐related fibrosis remain unclear. In this study, we induced rosacea‐like lesions in mice using LL‐37 and administered IL‐17A‐neutralizing antibodies. The results indicated that the IL‐17A‐neutralizing antibodies alleviated skin damage, reduced skin thickness, and decreased the secretion of inflammatory factors (TNF‐α, CAMP, TLR4, P‐NF‐kB), angiogenesis‐related factors (CD31, VEGF), and the TGF‐β1 signaling pathway, along with factors associated with epithelial–mesenchymal transition and the deposition of fibrosis‐related proteins (COL1) in the rosacea‐like mouse models. Furthermore, the IL‐17A‐neutralizing antibodies effectively diminished the expression of IL‐17, IL‐17R, CXCL5, and CXCR2 in the skin. Our findings demonstrate that IL‐17A‐neutralizing antibodies inhibit the activation of the CXCL5/CXCR2 axis in rosacea‐like skin tissue, thereby ameliorating inflammation and fibrosis associated with the condition.