bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human cytomegalovirus mediates APOBEC3B relocalization early during infection through a ribonucleotide reductase-independent mechanism
Authors: Fanunza Elisa , Cheng Adam Z. , Auerbach Ashley A. , Stefanovska Bojana , Moraes Sofia N. , Lokensgard James R. , Biolatti Matteo , Dell'Oste Valentina , Bierle Craig J. , Bresnahan Wade A. , Harris Reuben S. 
Published: August 2023

ABSTRACT
The APOBEC3 family of DNA cytosine deaminases comprises an important arm of the innate antiviral defense system. The gamma-herpesviruses Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus and the alpha-herpesviruses herpes simplex virus (HSV)-1 and HSV-2 have evolved an efficient mechanism to avoid APOBEC3 restriction by directly binding to APOBEC3B and facilitating its exclusion from the nuclear compartment. The only viral protein required for APOBEC3B relocalization is the large subunit of the ribonucleotide reductase (RNR). Here, we ask whether this APOBEC3B relocalization mechanism is conserved with the beta-herpesvirus human cytomegalovirus (HCMV). Although HCMV infection causes APOBEC3B relocalization from the nucleus to the cytoplasm in multiple cell types, the viral RNR (UL45) is not required. APOBEC3B relocalization occurs rapidly following infection suggesting the involvement of an immediate early or early (IE/E) viral protein. In support of this possibility, genetic (IE1 mutant) and pharmacologic (cycloheximide) strategies that prevent the expression of IE/E viral proteins also block APOBEC3B relocalization. In comparison, the treatment of infected cells with phosphonoacetic acid, which interferes with viral late protein expression, still permits A3B relocalization. These results combine to indicate that the beta-herpesvirus HCMV uses an RNR-independent, yet phenotypically similar, molecular mechanism to antagonize APOBEC3B.

IMPORTANCE
Human cytomegalovirus (HCMV) infections can range from asymptomatic to severe, particularly in neonates and immunocompromised patients. HCMV has evolved strategies to overcome host-encoded antiviral defenses to achieve lytic viral DNA replication and dissemination and, under some conditions, latency and long-term persistence. Here, we show that HCMV infection causes the antiviral factor, APOBEC3B, to relocalize from the nuclear compartment to the cytoplasm. This overall strategy resembles that used by related herpesviruses. However, the HCMV relocalization mechanism utilizes a different viral factor(s) and available evidence suggests the involvement of at least one protein expressed at the early stages of infection. This knowledge is important because a greater understanding of this mechanism could lead to novel antiviral strategies that enable APOBEC3B to naturally restrict HCMV infection.
Role of hospital leadership in pandemic preparedness: experience at a tertiary hospital in Kenya during the COVID-19 pandemic
Authors: Mwangi Lucy W , Macharia William , Wachira Benjamin W , Kimeu Jemimah , Mativa Boniface , Atwoli Lukoye 
Published: August 2023

IntroductionPandemic preparedness refers to being ready for, responding to and recovering from public health crises, and is integral for health security. Hospital leadership is a critical building block of an effective healthcare system, providing policy, accountability and stewardship in a health crisis.Objectives and methodsWe aimed to describe the leadership and governance structures put in place at the Aga Khan University Hospital, Nairobi, a private not-for-profit tertiary healthcare facility, following the COVID-19 pandemic. We reviewed over 200 hospital documents archived in the COVID-19 repository including those received from the Kenya Ministry of Health, emails, memos, bulletins, meeting minutes, protocols, brochures and flyers. We evaluated and described pandemic preparedness at the hospital under four main themes: (a) leadership, governance and incident management structures; (b) coordination and partnerships; (c) communication strategies; and (d) framework to resolve ethical dilemmas.ResultsThe hospital expeditiously established three emergency governance structures, namely a task force, an operations team and an implementation team, to direct and implement evidence-based preparedness strategies. Leveraging on partners, the hospital ensured that risk analyses and decisions made: (1) were based on evidence and in line with the national and global guidelines, (2) were supported by community leaders and (3) expedite financing for urgent hospital activities. Communication strategies were put in place to ensure harmonised COVID-19 messaging to the hospital staff, patients, visitors and the public to minimise misinformation or disinformation. An ethical framework was also established to build trust and transparency among the hospital leadership, staff and patients.ConclusionThe establishment of a hospital leadership structure is crucial for efficient and effective implementation of pandemic preparedness and response strategies which are evidence based, well resourced and ethical. The role of leadership discussed is applicable to healthcare facilities across low and middle-income countries to develop contextualised pandemic preparedness plans.
Trends of liposomal bupivacaine utilization in major lower extremity total joint arthroplasty in the USA: a population-based study
Authors: Stundner Ottokar , Hoerner Elisabeth , Zhong Haoyan , Poeran Jashvant , Liu Jiabin , Illescas Alex , Memtsoudis Stavros G 
Published: August 2023

IntroductionLiposomal bupivacaine has been marketed for the achievement of long-acting local or regional anesthesia after major lower extremity total joint arthroplasty. However, it is comparatively expensive and controversy remains regarding its ability to decrease healthcare costs. With mounting evidence suggesting non-superiority in efficacy, compared with plain bupivacaine, we sought to investigate trends in liposomal bupivacaine use and identify changes in practice.MethodsWe identified adult patients from the Premier Healthcare Database who underwent elective total joint arthroplasty between 2012 and 2021. Prevalence and trends of liposomal bupivacaine utilization were compared on the individual patient and hospital levels. Log-rank tests were performed to assess the influence of location, teaching status, or hospital size on time to hospital-level liposomal bupivacaine termination.ResultsAmong 103,165 total joint arthroplasty cases, liposomal bupivacaine use increased between 2012 and 2015 (from 0.4% to 22.8%) and decreased by approximately 1%–3% annually thereafter (15.7% in 2021). Liposomal bupivacaine was ever used in approximately 60% of hospitals. Hospital-level initiation of liposomal bupivacaine use peaked in 2014 and decreased thereafter (from 32.8% in 2013 to 4.3% in 2021), while termination rates increased (from 1.4% in 2014 to 9.9% in 2019). Non-teaching hospitals and those located in the South and West regions were more likely to retain liposomal bupivacaine longer than teaching or Midwest/Northeast hospitals, respectively (p=0.023 and p=0.014).DiscussionLiposomal bupivacaine use peaked around 2015 and has been declining thereafter on individual patient and hospital levels. How these trends correlate with health outcomes and expenditures would be a strategic target for future research.
Crowding out and impoverishing effect of tobacco in Mexico
Authors: Macías Sánchez Alejandra , García Gómez Adrián 
Published: August 2023

IntroductionTobacco is one of the world’s largest preventable causes of premature death, accounting for more than 8 million deaths and costing the global economy US$1.4 trillion each year. Smoking is a global problem with 1.3 billion people using tobacco worldwide, who will face harmful effects on health and on people’s current and future financial situations and quality of life.This article aims to be the first study to generate evidence on the effects of smoking on household expenditure and the number of people living under the poverty threshold by studying the crowding out and impoverishing effect in Mexico.MethodsThrough econometric methods and maximising a household utility function we estimate the crowding out and impoverishing effect of tobacco consumption in México based on household's income and spending survey from 2020.ResultsSpending on tobacco crowds out household spending on other goods and services. In Mexico, spending on tobacco results in decreased spending on essential goods and services, like education and healthcare, and increased spending on harmful goods such as alcoholic beverages. These effects are common across all income levels but are more pronounced in low-income households. When spending on tobacco increases, for example, following regular price increases made by the tobacco industry, the crowding out effect is exacerbated.In addition, smoking has an impoverishing effect on the population. This is because some families find that their remaining income level falls below the poverty line after deducting money spent on tobacco (a concept known as secondary poverty). In Mexico, 909 132 people are left with a disposable income level below the extreme poverty line because of expenditure on tobacco and smoking-related diseases.ConclusionsSmoking affects individual health and the finances of households in Mexico, particularly those of low-income people. By increasing tobacco taxes, those who quit smoking increase their quality of life and well-being. However, those who continue to smoke and increase their tobacco spending are affected by a shift in their spending on other goods and services.The increase in tobacco taxes must be accompanied by public policies that help reduce tobacco consumption and compensate the crowding out on goods and services relevant to the development of households.
Field study on installation effects of pre-bored grouted planted pile in deep clayey soil
Authors: Zhou Jia-jin , Yu Jian-lin , Gong Xiao-nan , Zhang Ri-hong 
Published: August 2023

This paper presents the results of field tests performed to investigate the installation effects of pre-bored grouted planted (PGP) pile in deep clayey soil. The variation of horizontal soil displacements, excess pore water pressures and lateral soil pressures was measured in the PGP pile installation process. The test results show that the drilling and grouting process induced large horizontal soil displacements in the soil within a radial distance of 2 d ( d is pile diameter), and the maximum horizontal soil displacements induced by the drilling and grouting process were smaller than 15.9 mm when the radial distance reached 4–5 d. Moreover, the horizontal soil displacements decreased along the soil layer depth, as the superficial soil layers were of small deformation modulus and lateral soil pressure. The drilling process brought large excess pore water pressures in the soil when the radial distance was less than 3 d, and the excess pore water pressures induced by the drilling stage were all less than 55 kPa when the radial distance reached 4–6 d. The drilling process also induced some lateral soil pressure increases in the soil within a radial distance of 3 d, while the measured maximum lateral soil pressure increases were smaller than 10.9 kPa when the radial distance increased to 4 d. On the whole, the excess pore water pressures and lateral soil pressure increases induced by the installation of PGP pile were much smaller than that induced by the installation of driven PHC pile. Moreover, the horizontal soil displacements, excess pore water pressures and lateral soil pressure increases induced by the installation of PGP pile all recovered rapidly after the installation of pile, as the cemented soil in the pile hole was in liquid state after the drilling and grouting stage.
Bilateral Oophorectomy and Colorectal Cancer Incidence and Mortality in the Women's Health Initiative
Authors: Song Mihae , Nelson Rebecca A. , Kruper Laura , Mortimer Joanne , Luo Juhua , Jung Su Yon , Wallace Robert B. , Chlebowski Rowan 
Published: August 2023

Abstract

Background:
The few cohort studies examining oophorectomy and colorectal cancer risk provide mixed results. Therefore, we examined this issue in Women's Health Initiative Observational Study participants.

Methods:
A total of 71,312 postmenopausal women were followed for 22.1 years (median). At enrollment, 55,643 (78%) had intact ovaries and 15,669 (22%) had undergone a bilateral oophorectomy. Colorectal cancers were verified by central medical record review with mortality findings enhanced by National Death Index queries.

Results:
With 1,421 incident colorectal cancers, 450 colorectal cancer-specific mortalities, after controlling for covariates, bilateral oophorectomy was not associated with colorectal cancer incidence or colorectal cancer mortality.

Conclusions:
No significant associations between oophorectomy and colorectal cancer incidence and mortality were seen in a large cohort study with long follow-up.

Impact:
As the oophorectomy and colorectal cancer question remains open, further studies of high quality, even with null findings, should be encouraged.
Diagnostic Performance of a Tumor Marker Gene Test to Personalize Serum CA19–9 Reference Ranges
Authors: Dbouk Mohamad , Abe Toshiya , Koi Chiho , Ando Yohei , Saba Helena , Abou Diwan Elizabeth , MacGregor-Das Anne , Blackford Amanda L. , Mocci Evelina , Beierl Katie , Dbouk Ali , He Jin , Burkhart Richard , Lennon Anne Marie , Sokoll Lori , Canto Marcia Irene , Eshleman James R. , Goggins Michael 
Published: August 2023

Abstract

Purpose:
CA19–9 synthesis is influenced by common variants in the fucosyltransferase (FUT) enzymes FUT3 and FUT2. We developed a clinical test to detect FUT variants, and evaluated its diagnostic performance for pancreatic ductal adenocarcinoma (PDAC).

Experimental Design:
A representative set of controls from the Cancer of the Pancreas Screening study was identified for each FUT functional group. Diagnostic sensitivity was determined first in a testing set of 234 PDAC cases, followed by a 134-case validation set, all of whom had undergone resection with curative intent without neoadjuvant therapy. Tumor marker gene testing was performed in the Johns Hopkins Molecular Diagnostics Laboratory. CA19–9 levels were measured in the Hopkins Clinical Chemistry lab. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminative ability of CA19–9 alone versus with the gene test.

Results:
Applying the CA19–9 standard cutoff (&lt;36 U/mL) to all 716 subjects yielded a 68.8% sensitivity in the test set of cases, 67.2% in the validation set, at 91.4% specificity. Applying 99th percentile cutoffs according to each individual's FUT group (3, 34.9, 41.8, and 89.2, for the FUT3-null, FUT-low, FUT-intermediate, and FUT-high groups, respectively) yielded a diagnostic sensitivity for CA19–9 in the first set of cases of 66.7%, 65.7% in the validation set, at 98.9% specificity. ROC analysis for CA19–9 alone yielded an AUC of 0.84; with the tumor marker gene test, AUC improved to 0.92 (P &lt; 0.001).

Conclusions:
Using a tumor marker gene test to personalize an individual's CA19–9 reference range significantly improves diagnostic accuracy.
Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial.
Authors: Salawu Abdulazeez , Wang Ben X. , Han Ming , Geady Caryn , Heirali Alya , Berman Hal K. , Pfister Thomas D. , Hernando-Calvo Alberto , Al-Ezzi Esmail Mutahar , Stayner Lee-Anne , Gupta Abha A. , Ayodele Olubukola , Lam Bernard , Hansen Aaron R. , Spreafico Anna , Bedard Philippe L. , Butler Marcus O. , Avery Lisa , Coburn Bryan , Haibe-Kains Benjamin , Siu Lillian L. , Abdul Razak Albiruni R. 
Published: August 2023

Abstract

Purpose:
Non-inflamed (cold) tumors such as leiomyosarcoma do not benefit from immune checkpoint blockade (ICB) monotherapy. Combining ICB with angiogenesis or PARP inhibitors may increase tumor immunogenicity by altering the immune cell composition of the tumor microenvironment (TME). The DAPPER phase II study evaluated the safety, immunologic, and clinical activity of ICB-based combinations in pretreated patients with leiomyosarcoma.

Patients and Methods:
Patients were randomized to receive durvalumab 1,500 mg IV every 4 weeks with either olaparib 300 mg twice a day orally (Arm A) or cediranib 20 mg every day orally 5 days/week (Arm B) until unacceptable toxicity or disease progression. Paired tumor biopsies, serial radiologic assessments and stool collections were performed. Primary endpoints were safety and immune cell changes in the TME. Objective responses and survival were correlated with transcriptomic, radiomic, and microbiome parameters.

Results:
Among 30 heavily pretreated patients (15 on each arm), grade ≥ 3 toxicity occurred in 3 (20%) and 2 (13%) on Arms A and B, respectively. On Arm A, 1 patient achieved partial response (PR) with increase in CD8 T cells and macrophages in the TME during treatment, while 4 had stable disease (SD) ≥ 6 months. No patients on Arm B achieved PR or SD ≥ 6 months. Transcriptome analysis showed that baseline M1-macrophage and B-cell activity were associated with overall survival.

Conclusions:
Durvalumab plus olaparib increased immune cell infiltration of TME with clinical benefit in some patients with leiomyosarcoma. Baseline M1-macrophage and B-cell activity may identify patients with leiomyosarcoma with favorable outcomes on immunotherapy and should be further evaluated.
Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance
Authors: Hanna Glenn J. , Roof Scott A. , Jabalee Jamie , Rettig Eleni M. , Ferrandino Rocco , Chen Sida , Posner Marshall R. , Misiukiewicz Krzysztof J. , Genden Eric M. , Chai Raymond L. , Sims John , Thrash Elaine , Stern Scott J. , Kalman Noah S. , Yarlagadda Sreenija , Raben Adam , Clements Lydia , Mendelsohn Abie , Kaczmar John M. , Pandey Yadav , Bhayani Mihir , Gupta Piyush , Kuperwasser Charlotte , Del Vecchio Fitz Catherine , Berger Barry M. 
Published: August 2023

Abstract

Purpose:
Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance.

Experimental Design:
This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5–154).

Results:
The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5–97.5] and 87.3% (95% CI: 79.1–95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9–99.8) and 98.4% (95% CI: 97.3–99.5), respectively.

Conclusions:
TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.
FOXN Transcription Factors: Regulation and Significant Role in Cancer
Authors: Song Jiali , Li Longshan , Fang Yang , Lin Yue , Wu Luojia , Wan Wei , Wei Gen , Hua Fuzhou , Ying Jun 
Published: August 2023

AbstractA growing number of studies have demonstrated that cancer development is closely linked to abnormal gene expression, including alterations in the transcriptional activity of transcription factors. The Forkhead box class N (FOXN) proteins FOXN1–6 form a highly conserved class of transcription factors, which have been shown in recent years to be involved in the regulation of malignant progression in a variety of cancers. FOXNs mediate cell proliferation, cell-cycle progression, cell differentiation, metabolic homeostasis, embryonic development, DNA damage repair, tumor angiogenesis, and other critical biological processes. Therefore, transcriptional dysregulation of FOXNs can directly affect cellular physiology and promote cancer development. Numerous studies have demonstrated that the transcriptional activity of FOXNs is regulated by protein–protein interactions, microRNAs (miRNA), and posttranslational modifications (PTM). However, the mechanisms underlying the molecular regulation of FOXNs in cancer development are unclear. Here, we reviewed the molecular regulatory mechanisms of FOXNs expression and activity, their role in the malignant progression of tumors, and their value for clinical applications in cancer therapy. This review may help design experimental studies involving FOXN transcription factors, and enhance their therapeutic potential as antitumor targets.
Деякі можливі шляхи оптимізації хірургічного лікування пахвиних гриж
Authors: Бенедикт В. В. , Продан А. М. , Лавренюк І. Ю. , Яцук К. Ю. 
Published: August 2023

Мета роботи: з метою покращення результатів хірургічного лікування пахвинних гриж розробити, поглибити та вдосконалити індивідуалізований підхід до операції в кожному конкретному випадку.
Матеріали і методи. Проведено комплексне обстеження 90 пацієнтів чоловічої статі хворих на пахвинну грижу віком 25–82 роки. У 30 хворих застосовано лапароскопічний метод лікування з використанням алопластичних матеріалів, 15 пацієнтам – герніопластику за Десардом, у 15 хворих використовували алопластичні матеріали за власною методикою (модифікація герніопластики Десарда) і у 30 випадках – герніопластику за Ліхтенштейном.
Результати досліджень та їх обговорення. Хірургічне лікування пахвинної грижі передбачає індивідульний підход до вибору способу пластики пахового каналу, що вимагає від хірурга знань в цьому питанні. При визначені методу хірургічного лікування пахвинних гриж необхідно брати до уваги загальний функціональний стан пацієнта і локальні зміни тканин пахвинної ділянки. При наявності технічних умов, компенсованому функціональному стані пацієнта (індекс коморбідності до 2 балів і операційно- анестезіологічному ризику за АSA<2 балів) можливе виконання лапароскопічних герніопластик. Модифікований метод хірургічного лікування за Десардом є ефективною альтернативою методу Ліхтенштейна.